Scientists say that for the first time they have been able to convertskin cells into pluripotent stem cells by activating the cells' own genes. The team reportedly used a type of CRISPRa gene-editing technology that does not cut DNA and can activate gene expression without mutating the genome.Up till now, reprogramming has only been possible by introducing the critical genes for the conversion, called Yamanaka factors, artificially into skin cells where they are not normally active.

The study (Human Pluripotent Reprogramming with CRISPR Activators)is published in Nature Communications.

CRISPR-Cas9-based gene activation (CRISPRa) is an attractive tool for cellular reprogramming applications due to its high multiplexing capacity and direct targeting of endogenous loci. Here we present the reprogramming of primary human skin fibroblasts into induced pluripotent stem cells (iPSCs) using CRISPRa, targeting endogenousOCT4,SOX2,KLF4,MYC, andLIN28Apromoters. The low basal reprogramming efficiency can be improved by an order of magnitude by additionally targeting a conserved Alu-motif enriched near genes involved in embryo genome activation (EEA-motif). This effect is mediated in part by more efficient activation ofNANOGandREX1,write the investigators.

These data demonstrate that human somatic cells can be reprogrammed into iPSCs using only CRISPRa. Furthermore, the results unravel the involvement of EEA [EGA-enriched Alu-motif]-motif-associated mechanisms in cellular reprogramming.

"CRISPR/Cas9 can be used to activate genes. This is an attractive possibility for cellular reprogramming because multiple genes can be targeted at the same time. Reprogramming based on activation of endogenous genes rather than overexpression of transgenes is also theoretically a more physiological way of controlling cell fate and may result in more normal cells. In this study, we show that it is possible to engineer a CRISPR activator system that allows robust reprogramming of iPSCs, saysTimo Otonkoski, M.D., Ph.D., at the University of Helsinki.

An important key for success was also activating a critical genetic element that was earlier found to regulate the earliest steps of human embryo development after fertilization. "Using this technology, pluripotent stem cells were obtained that resembled very closely typical early embryonal cells, addsJuha Kere, M.D., Ph.D., at the Karolinska Institute and King's College London.

The discovery also suggests that it might be possible to improve many other reprogramming tasks by addressing genetic elements typical of the intended target cell type.

The technology may find practical use in biobanking and many other tissue technology applications, notes doctoral student Jere Weltner, the first author of the article."In addition, the study opens up new insights into the mechanisms controlling early embryonic gene activation."

Read more here:
New CRISPR Approach Converts Skin Cells into Pluripotent ...

Recommendation and review posted by simmons

We have a lot of knowledge to share with you about stem cells and their value in skin care. We thought we would start with a current review of ongoing work in human stem cell science to give you some context. In the next few days we will be getting a lot more specific about wound healing, anti-aging, and related applications.

Human Stem Cells: Introduction

Future advances in many medical fields are thought to be dependent on continued progress in stem cell research. In this section, BTF briefly looks at the future of stem cell based therapies in the treatment of traumatic injury, degenerative diseases, and other ailments, and concludes with a review of current cell based therapies (stem cell and non-stem cell) in the field of skin care.

While the possible indications for stem cell based therapies are numerous,the field of stem cell science is young and years (or decades) may pass before todays promising laboratory results translate into useful clinical treatments. Only time will tell whether successes evolve or remain frustratingly elusive. We do know that success is possible.

The first stem cell therapy was bone marrow transplantation, originally accomplished in the mid 1960s. Last year, there were more than 50,000 such transplants worldwide. In earlier years, infusion of filtered bone marrow cells was performed with stem cells comprising but a very small part of the volume. Newer techniques have made it possible to separate cellular types to enable use of much higher concentrations of stem cells.

Much progress has been made in characterizing stem cells and understanding how they function. There is much more to the story than differentiation into tissue specific cells. Recent research shows that perhaps even more important is the fact that stem cells, especially certain types of stem cells, communicate with the cells around them by producing cellular signals called cytokines, of which there are hundreds.

Cytokines trigger specific receptors on cell membranes that result in precise responses. This phenomenon is considered an essential element in the healing response of all tissues. Identifying and characterizing the large number of cytokines is an important part of stem cell research.

Not every induced response is necessarily beneficial. It is the symphony of responses that is important. How to promote helpful responses while inhibiting non-beneficial ones is a continuing focus of cellular biochemical research as well as the basis upon which drug companies spend huge resources developing drugs to either trigger or block particular cytokine receptors. Good examples in the field of dermatology are EGFR (epidermal growth factor receptor) blocking compounds for use in treating susceptible cells, most notably cancers stimulated by EGF.

Potential Treatments

Stem cell therapies hold potential to treat many conditions and diseases that affect millions of people in the U.S.

From the Laboratory to the Bedside

Going from the research laboratory to the bedside takes time. Only one month ago, the FDA granted marketing approval for the first licensed stem cell product. Derived from donated umbilical cord blood, the product contains stem cells that can restore a recipients blood cell levels and function. In the chart below, the type of cells recovered from umbilical cord blood are those designated as HSC cell. They are the exact cells responsible for the success of bone marrow transplantation.

Of particular note are the cells designated in the chart as MSC or mesenchymal stem cells. MSC cells are the focus of intense research in the treatment of a number of conditions because this type of stem cell can differentiate into a variety of cell types including bone, cartilage, muscles, nerve, and skin (fibroblast.)

Recent announcements about stem cells being used to fabricate replacement parts (bone, cartilage, heart muscle) are based on MSC research. They truly are the duct tape of the bodys repair tool box; a phrase coined because of their importance in the healing of injuries.

Research has shown MSC cells reside in a number of tissues, including the bone marrow. Through precise chemical signaling that originate from sites of injury, MSC cells have the ability to become mobile, enter the blood stream and travel through the circulation to the injury. Upon arrival, MSCs orchestrate the healing response. Local resident stem cells are also called into action, to produce more stem cells or to produce needed tissue specific cells. In large part, MSCs accomplish their tasks bio-chemically.

Secreted cytokines have been identified as themajormechanism by which MSCs perform their important reparative functions. There are hundreds of cytokines identified thus far. The healing response is an intricate and balanced process in which many cytokines participate.

Despite their inherent ability to differentiate into essentially any type of cell, embryonic stem cells are unlikely to be a major research focus in the foreseeable future. Ethical and political considerations limit the acceptability of their use. Federal regulations permit research only on existing cell lines which are few in number. It is difficult to see how this prohibition will end any time soon.

Getting Closer butNot There Yet

MSC (mesenchymal stem cell) therapies include use ofcellsanduse of MSC factors, the cytokines or chemical messengers mentioned above. Methods of administration will likely include intravenous infusion, injections into tissues or body spaces, or development of drugs that activate or block certain cytokine effects. Drugs already in development include epidermal growth factor receptor (EGFR) blockers for use in cancer treatment.

Stem Cells and Skin Health

From fetal life to death, the numbers and activity of stem cells diminish. The chart at left shows how the population of mesenchymal stem cells in the bone marrow dwindles with age.

Knowing that stem cells are important in producing differentiated daughter cells (such as fibroblasts within the dermis) and are instrumental in orchestrating the bodys response to injury, it is easy to understand how skin damage from sun exposure, gravity, smoking, trauma, toxins, even repetitive facial movement, accumulates over time.

This is one line of evidence (we will look at others) that mesenchymal stem cells (or more specifically the relative lack of same) has a lot to do with aging. Skin aging included.

Products Claiming to Activate Skin Stem Cells

The number of skin products claiming to activate human skin stem cells is large and growing. As discussed previously on BFT, a whole slew of plant derived stem cell products are being marketing, NONE of which can actually or theoretically activate anything, especially not a human stem cell.

Other products claim to have essential nutrients or antioxidants or some other magical ingredient that will suddenly make stem cells take notice and unleash their regenerative power. It is highly unlikely, except in the most extreme case of malnourishment, that any nutrient or antioxidant is deficient enough to cause a cell not to function.

These and the botanical stem cell products are marketing ploys. Human stem cells deep within the dermis will never know whether or not these substances are applied. Moisturizers and other recognized ingredients in these products can be beneficial to skin appearancebut not because a stem cell is involved.

This is worse than junk science. This is scamming.

View original post here:
Skin & Human Stem Cells - BareFacedTruth.com

Recommendation and review posted by sam

What happened

Shares of the three companies pioneering medical applications of CRISPR gene-editing tools have soared higher through the first half of 2018. That's because, after years of only being able to discuss the possibilities of the technology, investors will soon be able to watch it (hopefully) progress through regulated clinical trials.

According to data from S&P Global Market Intelligence, CRISPR Therapeuticstops the trio with year-to-date gains of 169% and a market cap of nearly $3 billion. Intellia Therapeuticsis next with a 63% rise and a market cap of $1.3 billion. Editas Medicine, which has managed a 25% leap since the beginning of the year, is valued at $1.8 billion. It entered January as the most valuable of the three.

Image source: Getty Images.

All three companies are about to investigate their unique CRISPR tools in the clinic for the first time, and their respective stock performances thus far this year correlate with how close each is to initiating clinical trials.

CRISPR Therapeutics is the furthest along, looking to begin clinical trials for its lead drug candidate, CTX001, as a treatment for blood diseases such as sickle cell by the end of this year. While it was placed on a clinical hold by the U.S. Food and Drug Administration at the end of May, the company and its partner Vertex will proceed with a phase 1/2 trial in Europe as planned. Not wanting to rest on its lead, the company is looking to file its second investigational new drug (IND) application by the end of 2018.

Meanwhile, Editas Medicine told investors it would file an IND for its lead drug candidate in mid-2018, so investors should expect that news any day now. The company will first take aim at LCA10, a rare eye disease.

Intellia Therapeutics is furthest behind, as it doesn't expect to file an IND until the end of 2019. That could work out in the company's favor in the long run, however, as it's working on a novel delivery system (one of the biggest question marks for all three companies) to increase the efficacy and safety of its therapeutics, the first of which will be evaluated to treat a rare metabolic disease called transthyretin amyloidosis.

Company

End Q1 2018 Cash Balance

IND Filing Guidance

CRISPR Therapeutics (NASDAQ:CRSP)

$342 million

Initiating first clinical trial by end of 2018, second IND by end of 2018

Editas Medicine (NASDAQ:EDIT)

$359 million

Mid-2018

Intellia Therapeutics (NASDAQ:NTLA)

$328 million

End of 2019

Data source: Company disclosures.

All three stocks have largely brushed off concerns raised in June that CRISPR tools could potentially set off existing and potentially cancerous mutations within cells. While none of the lead drug candidates would be affected by the approaches being used, all three pipelines will have to navigate that obstacle eventually.

Investors are betting that gene editing will become a game changer in medicine -- and they might be right. However, it's important to remember that CRISPR tools are still in their infancy in the clinic. There are still questions about optimal delivery of the therapeutic payload into human cells in a patient, the best cutting enzyme, and the triggering of DNA repair mechanisms being relied on to finish the genetic surgery procedure. Each has implications for the efficacy and safety of the technology.

Considering these questions (and more) will find their first answers in clinical trials that have yet to begin, and the fact these companies are valued at up to $3 billion, investors should understand the high level of risk involved with CRISPR stocks at this point in development. There could be a long way to go before reality matches the hype.

Maxx Chatsko has no position in any of the stocks mentioned. The Motley Fool owns shares of CRISPR Therapeutics. The Motley Fool recommends Editas Medicine. The Motley Fool has a disclosure policy.

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Here's Why CRISPR Stocks Have Gained as Much as 169% in 2018 ...

Recommendation and review posted by Bethany Smith

Alternative names for male hypogonadism

Testosterone deficiency syndrome; testosterone deficiency; primary hypogonadism; secondary hypogonadism; hypergonadotrophic hypogonadism; hypogonadotrophic hypogonadism

Male hypogonadism describes a state of low levels of the male hormone testosterone in men. Testosterone is produced in the testes and is important for the formation of male characteristics such as deepening of the voice, development of facial and pubic hair, and growth of the penis and testes during puberty. Gonadotrophin-releasing hormone, made in the hypothalamus, stimulates the pituitary gland to produce luteinising hormone and follicle stimulating hormone (gonadotrophins). The gonadotrophins then act on the testes causing them to produce testosterone.Low levels of testosterone can occur due to disease of the testes or from conditions affecting the hypothalamus or pituitary gland. Men can be affected at any age and present with different symptoms depending on the timing of the disease in relation to the start of puberty. In some cases, it can be difficult to tell if there is a true deficiency of testosterone, particularly when the levels are in the borderline range.

Male hypogonadism can be divided into two groups.Classical hypogonadism is where the low levels of testosterone are caused by an underlying specific medical condition, for example Klinefelter's syndrome, Kallmanns syndrome or a pituitary tumour.Late-onset hypogonadism is where the decline in testosterone levels is linked to general ageing and/or age-related diseases, particularly obesity and type 2 diabetes.It is estimated that late-onset hypogonadism only affects about 2% of men over the age of 40.

There are two types of classical male hypogonadism primary and secondary.Primary hypogonadism occurs when the low level of testosterone is due to conditions affecting the testes.Primary hypogonadism is also referred to as hypergonadotrophic hypogonadism, whereby the pituitary produces too much luteinising hormone (LH) and follicle stimulating hormone (FSH) (gonadotrophins) to try and stimulate the testes to produce more testosterone. However, as the testes are impaired or missing, they are not able to respond to the increased levels of gonadotrophins and little or no testosterone is produced. In some patients with primary hypogonadism, testosterone levels may be within the normal range, but the increased LH and FSH indicates that the pituitary gland is trying to compensate for a deficiency and treatment may still be needed.

Examples of conditions affecting the testes, which lead to primary gonadal failure, include:

Secondary hypogonadism results from conditions affecting the function of the hypothalamus and/or pituitary gland.It is also known as hypogonadotrophic hypogonadism due to low levels of LH and FSH resulting in decreased testosterone production.Secondary hypogonadism often occurs as part of a wider syndrome of hypopituitarism.Examples of causes can include:

The signs and symptoms depend on the stage at which the patient presents with hypogonadism in relation to sexual maturity.If testosterone deficiency occurs before or during puberty, signs and symptoms are likely to include:

Around the time of puberty, boys with too little testosterone may also have less than normal strength and endurance, and their arms and legs may continue to grow out of proportion with the rest of their body.

In men who have already reached sexual maturity, symptoms are likely to include:

As some of these symptoms (e.g. tiredness, mood changes) can have multiple causes, diagnosis of male hypogonadism may sometimes get missed initially.

Male hypogonadism is more common in ageing men. The levels of testosterone in men start to fall after the age of 40. It has been estimated that 8.4% of men aged 5079 years have testosterone deficiency.Male hypogonadism is also linked with type 2 diabetes: approximately 17% of men with type 2 diabetes are estimated to have low testosterone levels.

Male hypogonadism does not run in families.There are genetic causes of hypogonadism, which include Klinefelters syndrome and Kallmanns syndrome; however, these conditions occur sporadically, they are not inherited from the parents.

A detailed medical history should be taken.In particular, it is important to find out if virilisation (development of normal male characteristics) was complete at birth, whether the testes descended and to see if the patient went through puberty at the same time as his peers. The patient should be thoroughly examined and the presence and size of the testes recorded, and whether they are correctly positioned in the scrotum.

Many of the symptoms of male hypogonadism are non-specific and can be caused by a range of conditions. Therefore, when diagnosing hypogonadism, it is important that biochemical tests are performed to assess the levels of testosterone in the blood to confirm diagnosis. Blood tests will be carried out to measure testosterone levels.The blood sample should be collected preferably at 9 a.m. (this is because levels of testosterone change throughout the day) and in the fasting state (because eating can lower testosterone leves). The blood test can can be carried out as an outpatient appointment. If the result of the first test shows a low level of testosterone, the test should be repeated after two or three weeks to confirm the result. Other hormones are also tested along with the second blood sample. These hormones include luteinising hormone, follicle stimulating hormone and prolactin (produced by the pituitary gland).The results of these blood tests will help distinguish between primary (low testosterone and high gonadotrophins) and secondary (low testosterone and normal or low gonadotrophins) hypogonadism.Testosterone is carried around the blood stream by a protein called Sex Hormone Binding Globulin (SHBG). SHBG is often checked at the same time as testosterone as it makes it easier to interpret whether there is a true deficiency. In patients with obesity and type 2 diabetes, SHBG is often low which can make the testosterone level appear lower than it really is.

Depending on the findings of the above tests, other investigations may be carried out. These include: a bone densitometry test to assess the impact of testosterone deficiency on bone; semen analysis; genetic studies; and an ultrasound of the testes to check for nodules or growths.

Treatment of classical hypogonadism involves replacement of testosterone with the aim of raising the level of testosterone in the blood to normal levels.Exact treatment will vary between patients and be tailored to their individual needs.Different preparations of testosterone are available:

All these are outpatient treatments. All of these options should be discussed with a medical professional and the most appropriate treatment option chosen.During treatment with testosterone replacement, regular blood tests should be carried out to monitor testosterone levels and if necessary, the dose adjusted to ensure levels return to the normal range.Tablet forms of testosterone taken by mouth are not recommended due to a link with liver damage, and because it is more difficult to monitor replacement.

Testosterone should not be given if the patient has prostate cancer, because it might make the tumour grow quicker. Before starting treatment with testosterone, a blood test to measure a hormone produced by the prostate called PSA (prostate-specific antigen) is carried out (PSA levels are elevated in prostate cancer).The prostate may also be examined (via the back passage) to rule out prostate cancer.

For patients who have been diagnosed with late-onset hypogonadism, there is currently not enough evidence for us to know whether treatment with testosterone is safe and effective over the long term.While there are some short-term studies that indicate it may benefit these patients over a short period of time, there is a need for longer-term clinical trials in this area, following a large number of patients, to assess the long-term impact of testosterone treatment on patients with late-onset hypogonadism. Areas that particularly require focus are assessing the effects of treatment on the likelihood of developing cardiovascular disease, prostate cancer and secondary polycythaemia (a condition in which there are increased numbers of red blood cells in the blood, which may predispose to increased blood clots).

If patients have any concerns about their health, they should contact their GP in the first instance.

There can be mild side-effects of testosterone replacement depending on the form used: injectable forms can cause pain and bruising at site of injection; the gel form can cause skin irritation.

Treatment with testosterone can cause an increase in red blood cells (known as polycythaemia), which increases the risk of thrombosis.Regular blood tests should be carried out during treatment to check for an increase in red blood cells.Enlargement of the prostate is another serious side-effect that should be monitored.Prostate examination and a blood test for PSA should be performed every three months for the first year and then annually in men over the age of 40 years after starting treatment.If patients have any concerns about these possible side-effects, they should discuss them with their doctor.

Symptoms of male hypogonadism, such as lack of sex drive, inadequate erections (erectile dysfunction) and infertility, can lead to low self-esteem and cause depression. Professional counselling is available to help deal with these side-effects; patients should talk to their doctor for more information.Patients generally see an improvement in their sex drive and self-esteem following testosterone replacement therapy. Erectile dusfunction is a common symptom in patients without hypogonadism and may need treatment in addition to testosterone.

Male hypogonadism has been linked with an increased risk of developing heart disease (low testosterone can cause an increase in cholesterol levels). Studies have shown that testosterone levels can be lower in men with type 2 diabetes and in men with excess body weight. However, it is not clear whether this is an association or a direct cause and effect. Lifestyle changes to reduce weight and increase exercise can raise testosterone levels in men with diabetes.

Testosterone levels in men decline naturally as they age.In the media, this is sometimes referred to as the male menopause (andropause) although this is not a generally accepted medical term.Low testosterone levels can also cause difficulty with concentration, memory loss and sleep difficulties.Current research suggests that this effect occurs in only a small group of ageing men.However, there is a lot of research in progress to find out more about the effects of testosterone in older men and also whether the use of testosterone replacement therapy would have any benefits.

Last reviewed: Mar 2018

Read more from the original source:
Male hypogonadism - You and Your Hormones

Recommendation and review posted by Bethany Smith

CTERP INTERNATIONAL CONFERENCEApril 11-13, 2018Moscow, Russia

In recent years there have been rapid advances in applying the discoveries in cell technologies field into medical practice. Cell technologies are progressing as the result of multidisciplinary effort of scientists, clinicians and businessmen,with clinical applications of manipulated stem cells combining developments in transplantation and gene therapy.Challenges address not only thetechnology itself but also compliancewith safety and regulatory requirements.

The Conference will provide a platform for scientists from basic and applied cell biology fields, practical doctors, and biotech companies to meet and share their experience, to discuss the research associated with developing biomedical clinical products and translating this research into novel clinical applications, challenges of such translational efforts and foundation of bioclusters assisting further developments in cell technology.

The official language of the conference is English.

Conference materials will be published in the Russian Journal of Developmental Biology.

Please download your abstracts in accordance with the journal guidelines (english, russian) for authors provided on their website.

Excerpt from:
CTERP International Conference - 2018: About

Recommendation and review posted by Jack Burke

Purpose of Study

The Newcastle University and the University of Rochester, in collaboration with the United States National Institutes of Health, and the National Institute of Neurological Disorders and Stroke, are conducting a phase III study with corticosteroids in boys with Duchenne Muscular Dystrophy (FOR DMD study).

Corticosteroids are currently the only medicine that has been shown to increase muscle strength in boys with DMD. Doctors have tried different ways of prescribing corticosteroids in order to decrease undesirable side effects. Currently, different doctors in different countries prescribe the drugs in different ways, and some do not prescribe corticosteroids at all.

The FOR DMD study aims to compare three ways of giving corticosteroids to boys with DMD to determine which increases muscle strength the most, and which causes the fewest side effects.

Using the results of this study, we aim to provide patients and families with clearer information about the best way to take these drugs.

This study will look at three ways of taking corticosteroids by the mouth:

All three dosages are commonly used in boys with DMD and have shown to be beneficial.

In this study there is no placebo group, which means that all participants will receive active drugs (Prednisone or Deflazacort). However, neither the boys nor the clinicians will know which treatment or regime the boy is taking.

The study will recruit 300 boys around Europe, United States and Canada.

In North America, 16 centers will take part in the study:

Patients who do not attend one of these hospitals for their routine follow-up can also participate, but will have to travel to their closest participating site to receive the study drug and for the check-ups.

Participants will receive study medication for a minimum of three years and a maximum of five years (depending on how early the boy was recruited into the study) and participation involves visits to the study hospital every three months for the first 6 months and every six months thereafter. At these visits we will be repeating many of the tests your child usually has in clinic for his routine DMD follow up.

Who can participate:

In order to take part in the study boys need to fulfil a number of criteria. These can only be checked when you come into the clinic. However, at this stage if your child may be eligible if he:

Who to contact:

If you feel that your child might be able to participate in this trial, please feel free to discuss it with your doctor locally. Alternatively, if you would like further information, please contact the University of Rochester Medical Center: Kim Hart | Phone: 1 (585) 275-3767.

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Gene Therapy Clinical Research - nationwidechildrens.org

Recommendation and review posted by simmons

If you read my blog or follow my work, you know that my mission is to help women weed through the myths and mysteries to uncover the truth: how to eat, how to move and how to live so you thrive in that powerful place of physical, mental and emotional well-being.

But at the end of the day, many of you still have health issues you have to address with conventional medicine. If youre lucky, you have a caring and committed physician who is willing to guide you in the process. If youre not so lucky? You can end up feeling frustrated and alone when your doctor doesnt listen to your concerns or when youre thrown yet another prescription for something that may or may not help you get better.

If you suspect you have a hormonal imbalance but youre concerned about how to approach your doctor, youre not alone. While I specialize in these types of issues, many general physicians may not investigate this area as a first plan of attack to treat health problems.

So what do you do when youre ready to broach the subject? How can you get the right answers, take the right tests and know that your doctor is on your side?

If youre willing to be candid, a little preparation can help you open the lines of communication and hopefully lead you to better health outcomes.

Doctors are no different from other working professionals who see clients or patients. Their time is usually limited, so its important to make the most of your appointment. A good step for initial preparation is to take my hormone quiz (you can access it online or in my book, The Hormone Cure). The results of this assessment should give both you and your doctor a general idea of what hormonal imbalances might be at play. With a few follow-up questions, your physician should be able to determine what tests might be needed to investigate the problem further.

It never hurts to present a physician with your own research on the topic that concerns you. If youve done your homework, feel free to bring along books, studies or other materials on the subject. This can help start the conversation, letting your doctor know that youre informed and serious about getting answers. Another research step you can take is to complete a comprehensive hormonal profile test at home (which can be purchased through the Canary Club) and take the results to your appointment.

If youve taken preliminary tests, done your research or have some other reason to suspect a problem (maybe you have a family history of low thyroid or an autoimmune condition, for example), dont be afraid to ask for specific tests. If, on the other hand, youre going into the conversation with little information, bring along a list of specific questions. You can then compare your doctors answers to your own research or you can get a second opinion.

If youre not confident in your physicians ability to help you address your concerns, its always OK to ask for a referral to an endocrinologist or someone who has more experience treating hormonal imbalance. You may also need to simply shop around for a doctor with whom you feel comfortable and supported.

While some physicians are great at blending traditional medicine with more holistic approaches, you might need to turn elsewhere for support in areas like nutrition, herbal medicine or natural hormone balance. It may be possible to work with your doctor but also to get support from a health coach, a nutritionist or some other type of practitioner who has the necessary qualifications. This might require a more proactive stance on your end youll need to make sure youre communicating important information with both the doctor and the practitioner (like your health history, supplements or herbs youre taking, etc.) But this type of combined approach can work if youre doing it safely and consulting both parties about the treatment youre receiving.

Finding a good doctor is like finding a good therapist, a good friend or a good job it can take some time and effort. Do your research, read patient reviews and study a physicians background, qualifications and approach before you even have a consultation. Like any other relationship, when its right, youll know.

Lastly, remember that the biggest advocate for your own treatment and care should be you. Ask the tough questions, be assertive and follow up your health may depend on it.

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Hormone Questions? Ask Your Doctor These 6 Things | Sara ...

Recommendation and review posted by Bethany Smith

Three of the most well-known genes that can mutate and raise the risk of breast and/or ovarian cancer are BRCA1, BRCA2, and PALB2. Women who inherit a mutation, or abnormal change, in any of these genes from their mothers or their fathers have a much higher-than-average risk of developing breast cancer and/or ovarian cancer. (Abnormal PALB2 genes are suspected to raise the risk of ovarian cancer, but larger studies need to confirm that risk.) Men with these mutations have an increased risk of breast cancer, especially if the BRCA2 gene is affected, and possibly of prostate cancer. Many inherited cases of breast cancer have been associated with mutations in these three genes.

The function of the BRCA and PALB2 genes is to keep breast cells growing normally and prevent any cancer cell growth. But when these genes contain the mutations that are passed from generation to generation, they do not function normally and breast cancer risk increases. Abnormal BRCA1, BRCA2, and PALB2 genes may account for up to 10% of all breast cancers, or 1 out of every 10 cases.

Most people who develop breast cancer have no family history of the disease. However, when a strong family history of breast and/or ovarian cancer is present, there may be reason to believe that a person has inherited an abnormal gene linked to higher breast cancer risk. Some people choose to undergo genetic testing to find out. A genetic test involves giving a blood or saliva sample that can be analyzed to pick up any abnormalities in these genes.

In this section, you can read more about the following topics related to genetic testing:

If you want to learn more about family-related risk and genetics, you can visit the Lower Your Risk section of this site.

Researchers have discovered, and are continuing to discover, other abnormal genes that are less common than BRCA1, BRCA2, and PALB2 but also can raise breast cancer risk. Testing for these abnormalities is not done routinely, but it may be considered on the basis of your family history and personal situation. You can work with your doctor to decide whether testing for gene abnormalities besides BRCA1, BRCA2, and PALB2 is warranted.

The medical experts for Genetic Testing are:

These experts are members of the Breastcancer.org Professional Advisory Board, which includes more than 70 medical experts in breast cancer-related fields.

"Simply having a proven gene abnormality does not necessarily mean that a woman will develop breast cancer, or that her cancer will be any worse than cancer that does not stem from an inherited genetic flaw."

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Genetic Testing: BRCA1, BRCA2, and PALB2 Mutations

Recommendation and review posted by Bethany Smith

Melissa Franklin Professor of Physics, Harvard University "I build things, and then I fix them when I build them badly," says the experimental physicist, offering a deceptively modest description of her work. The objects she tinkers with are complex particle detectors, including the powerful proton-antiproton Collider Detector at Fermilab in Batavia, Illinois, which she used to spot the top quark in 1995.

Maria Zuber Professor of Geophysics and Planetary Science, MIT Using laser ranging, gravity measurements, and data from spacecraft, Zuber maps surface features and probes the interior of Mars, Venus, Jupiter's moons, and our own moon. Her goal is to "figure out the processes that acted on a particular body in the past in order to make its surface the way it is now."

Fame Passed Them By

History has not always been kind to women scientists. Many have passed long days and nights in the lab stirring noxious concoctions or gathering piles of data only to see the credit for their discoveries awarded to a male colleague. Sometimes the work was obscured by a famous mentor. Here is a selection of female scientists who deserve greater notice:

Lise Meitner (1878-1968) In 1938, after she escaped from the Nazis to Sweden, she carried out the key calculations that led to the discovery of nuclear fission. Her collaborator, Otto Hahn, who stayed behind in Germany, was the sole recipient of the Nobel Prize in chemistry in 1944. In 1997 Meitner was finally honored when element 109 was named meitnerium.

Emmy Noether (1882-1935) She devised a mathematical principle, called Noether's theorem, which became a foundation stone of quantum physics. Her calculations helped Einstein formulate his general theory of relativity. "It is really through her that I have become competent in the subject," he admitted.

Frieda Robscheit-Robbins (1893-1973) Together with George Whipple, she discovered that a diet rich in liver cured anemia in dogs, which in turn led directly to treatment for pernicious anemia in humans. Although she coauthored numerous papers with Whipple, it was he who was honored with the 1934 Nobel Prize in medicine.

Hilde Mangold (1898-1924) Under the guidance of Hans Spemann, she carried out the experiments that led to the discovery of the organizer effect, which directs the development of embryonic cells into tissues and organs. She died after being set afire by an alcohol stove on which she was heating food for her baby. Eleven years later, Spemann won the Nobel Prize.

Cecilia Payne-Gaposchkin (1900-1979) In her 1925 Ph.D. thesisdescribed by the noted astronomer Otto Struve in 1960 as "the most brilliant . . . ever written in astronomy"she proposed that all stars are made mostly of hydrogen and helium. Astronomers dismissed her observations until four years later, when they were confirmed by a man. She was the first woman to become a professor of science at Harvard.

Beatrice "Tilly" Shilling (1909-1990) A prize-winning motorcycle racer and aeronautical engineer, she designed a small metal ring that fit onto the fuel line of an aircraft engine to keep the flow of fuel constant. This enabled World War II British fighter pilots to dive without fear that their engines would cut out.

Chien-Shiung Wu (1912-1997) In 1957 she and her colleagues overthrew a principle previously considered immutable in physics: that nature does not distinguish between right and left. Chien-Shiung found that this rule does not hold true for interactions between subatomic particles involving the so-called weak force. The Nobel Prize was awarded to two male colleagues.

Rosalind Franklin (1920-1958) Her X-ray photographs of crystallized DNA, taken in the early 1950s, proved that the molecule was a helix. This data was used, without her knowledge, by James Watson and Francis Crick to elucidate the structure of DNA. By the time they were awarded the Nobel Prize in 1962, Franklin had died of ovarian cancer.

Jocelyn Bell Burnell (1943-) With the aid of a radio telescope she built herself, she became the first astronomer to detect pulsarsrapidly spinning, extremely dense neutron stars. But she was deemed too inexperienced to receive the Nobel Prize, which was given instead in 1974 to her thesis adviser, Anthony Hewisha man who later referred to her as "a jolly good girl [who] was just doing her job."

Josie Glausiusz

Originally posted here:
The 50 Most Important Women in Science - Discover Magazine

Recommendation and review posted by simmons

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The key stages of female hormones and how hormonal imbalance affects your body.

Index:

You inhabit an amazing body that performs a myriad of functions every second of the day. This incredible feat is controlled by your brain and co-ordinated by your hormones. Millions of women are affected by hormonal changes throughout their lives but have little idea about how or why. Hormonal imbalances can lead to:

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Hormones are essentially chemical messengers secreted by endocrine glands in the body that are designed to adjust metabolic functions in cells. They do this by regulating the production of a specific protein or by activating enzymes.

There are two basic types of hormones, steroid and peptide. They travel to their target organs in the bloodstream and work in complicated harmony to maintain balance at all times. Steroid hormones are fat soluble compounds that can easily pass through cell membranes.

Some of these include:

Peptide hormones are water soluble compounds that are able to dissolve in the blood in order to be transported around the body. Some of these include:

Hormones are secreted by the endocrine system which is largely controlled by the pituitary gland - in the brain - under the direction of the hypothalamus.

Hormone balance (Homeostasis) is maintained by a key regulatory mechanism called negative feedback which either opposes the release of certain hormones or causes hormones to act antagonistically by opposing each others actions.

For example if blood sugar (glucose) levels are too high the brain sends a signal to release insulin which lowers blood glucose. If blood glucose levels drop too low the brain triggers the release of glucagon which raises blood sugar.

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Hormones co-ordinate many diverse areas including:

When the correct balance of hormones is maintained most daily challenges are met and the body thrives, but if levels are too high or low it can lead to health problems such as thyroid disease, polycystic ovaries, endometriosis, infertility, fibroids, depression and acne.

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Female hormones exist primarily to promote growth and reproduction and have a significant effect on a womans development throughout her life. The two main female hormones, oestrogen and progesterone are produced predominantly in the ovaries but also in the adrenal glands which sit just above the kidneys.

At puberty oestrogen is responsible for the development and maturation of the uterus, fallopian tubes, breasts and vagina. It also plays a key role in the growth spurt and deposition of fat around the buttocks, hips and thighs.

There are at least six different oestrogens, however only three are synthesised in significant amounts:

Beta-estradiol, Estrone & Estriol.

Progesterone is involved in regulating the menstrual cycle and is vital for supporting a healthy pregnancy. It is also particularly important for balancing and controlling oestrogen performance, opposing some of the powerful effects of excess oestrogen. For instance oestrogen triggers release of the stress hormone cortisol while progesterone counters it.

Oestrogen stimulates cell growth, while progesterone ensures growth is maintained at healthy levels. Low progesterone levels lead to uncontrolled oestrogen which results in hormonal imbalances. Low levels of progesterone may affect:

Women also produce a little testosterone (normally considered a male hormone) from their ovaries, which helps to promote muscle mass and bone growth. These levels naturally decline post menopause.

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Puberty:

During this stage the ovaries are stimulated by luteinising hormone (LH) and follicle-stimulating hormone (FSH) which are secreted by the pituitary gland under the influence of the hypothalamus.

These hormones bring about the physical changes associated with puberty. Menstruation usually occurs around the time that a womans growth spurt slows down. The whole process takes around 4 years.

Pregnancy:

This is a time when a womans hormones change dramatically:

Menopause:

The lead up to the menopause (the peri-menopause) starts around the age of 40 and ends on average at age 52. Whilst there are considerable hormonal changes that occur during puberty and the childbearing years - the menopause and post menopause seem to be the most problematic. This life stage can be extremely challenging for some women.

Oestrogen plays a vital role in protecting the heart, bones, bladder and vagina as well as maintaining the breasts. Lack of oestrogen and progesterone during the menopause can create hormonal imbalances which have significant consequences for health with an increased risk of osteoporosis and heart disease and can also result in a range of distressing symptoms.

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The ratio between oestrogen and progesterone is critical for the maintenance of homeostasis. Often the effects of high oestrogen are due to a combination of mildly high oestrogen levels together with a mild progesterone deficiency.

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An increase in the ratio of oestrogen to progesterone can lead to:

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Hormone function can be disrupted if too much of a hormone is produced or too little. This may be due to a number of factors including:

Malnutrition

Undereating, a poor diet, insufficient calories and nutrients, reliance on stimulants and junk food can lead to a nutrient deficiency which will ultimately affect hormone production. For example, Studies have found that B6 supplementation has positive effects on some PMS symptoms. It is likely that B6 helps to balance oestrogen and progesterone levels mid cycle. B6 is also a co-factor in the synthesis of serotonin.

Being underweight with insufficient fat reduces cholesterol which is needed to produce sex and stress hormones. During the menopause oestrogen is produced in the abdominal fat cells as ovarian function diminishes.

Poor liver function

Oestrogen has to be metabolised by the liver and excreted in bile. If the liver is not functioning efficiently oestrogen levels in the blood may remain relatively high.

Overloading the liver with alcohol, drugs, caffeine and chemicals in food may lead to poor liver function.

Certain Foods

Too much sugar, alcohol, chocolate, fried foods, trans fats and refined carbohydrates can affect liver function which could contribute to higher oestrogen levels.

Constipation

Before used oestrogen can be eliminated via the stool it has to be modified by intestinal bacteria and bound to fibre. This bulks out the stool and encourages normal bowel movements.

Good levels of healthy gut bacteria and plenty of dietary fibre are essential for this process otherwise the used oestrogen may be recirculated.

Chemicals in food

Certain chemicals such as pesticide residues found in non-organic dairy and meat products can mimic oestrogens in the body.

Oestrogens are also included in cattle feed to fatten them up.

Environmental factors and xenoestrogens

There are many petrochemical products that affect the balance of hormones in the body. These include:

Alkylphenol ethoxylates in detergents and emulsifiers; nonylphenol ethoxylates used as spermicides and plasticisers; bisphenols used in certain industrial and chemical processes and dental fillings, the birth control pill and HRT

Genetics

There may be a family history of early menopause or low thyroid function.

Read more:
12 Female Hormones Facts - Understanding your Hormones Today

Recommendation and review posted by Bethany Smith

Hypogonadism (hi-po-go-na-dizm) also known as low testosterone (Low T),occurs when the body does not produce enough male sex hormones (androgen deficiency), specifically testosterone, and it can result in sexual impotence, infertility, loss of muscle mass and strength, reduction in bone density, mood changes and fat accumulation. It can develop from a testicular disorder at any age or it can result from disease, injury or drug abuse.

There are two basic types of male hypogonadism, which both result in decreases in sperm and testosterone production.

Primary hypogonadism is low testosterone due to a dysfunction or defect in the testes.

Secondary hypogonadism is low testosterone due to a dysfunction or defect in the pituitary gland or hypothalamus (the parts of the brain that signal the testicles to produce testosterone).

What is Testosterone?

Testosterone is the most important sex hormone in the male body. It is needed for masculine growth and development during puberty, and the development of male characteristics such as body and facial hair, muscle growth, strength and a deep voice. Normal levels of testosterone also influence the production of sperm, promote sexual function and sex drive. The brain and the testicles work together to keep testosterone levels within a normal range. When levels of testosterone are below normal, the brain signals the testicles to make more. When testosterone levels are too high, the brain signals for the testicles to make less.

TESTOSTERONE & AGING

The ability to produce testosterone declines as men age, resulting in a condition called hypogonadismor Low Testosterone (Low T). This loss of testosterone may lead to uncomfortable and distressing symptoms. Researchers estimate that hypogonadism affects from 2-6 million men in the United States with only 5% receiving treatment.*

Low T may affect a mans interest in sex, his ability to perform sexually and it can result in sexual impotence, infertility, loss of muscle mass and strength, reduction in bone density, mood changes and fat accumulation. Causes of Low T vary, and some men are born with the condition, while others develop it later in life. Low T is characterized by low levels of testosterone and presents such symptoms such as decreased sexual desire, erectile dysfunction, decreased energy and depression.

Its normal for a mans sex drive to slowly decline from its peak in his teens and 20s, but libido and sex drive vary widely among men and also for an individual over time. It is affected by stress, sleep, general health and opportunities for sex. Men may not recognize a problem until a partner considers it an issue or the man recognizes he cannot function sexually.

In Puberty:Hypogonadism may delay puberty or inhibit development. You may notice the following symptoms:

In Adulthood:Hypogonadismmay alter physical characteristics, cause health problems or impair reproductive function. You may notice the following symptoms.

Some men may also experience the following signs and symptoms:

CAUSES OF HYPOGONADISM IN MEN INCLUDE:

GET SCREENEDYou may want to ask your healthcare provider to check you for low testosterone levels if you experience symptoms associated with Low T. A primary care provider checks testosterone levels with a blood test to determine if you have Low T and determine if testosterone therapy is right for you. You might also ask your healthcare provider about a referral to an endocrinologist or urologist who specializes in treating Low T.

In order to get the best treatment, its important that you become a proactive partner in your healthcare. Here are some questions you can ask your healthcare provider about Low Testosterone.

If you do experience symptoms of Low Testosterone and are diagnosed by a healthcare provider, the good news is that the condition very often is treatable.

There are several FDA-approved testosterone replacement therapies, including:

Gels and SolutionsTestosterone gels and solutions are applied directly to the skin and are absorbed into the body. These generally require daily application.

PatchesPatches allow testosterone to be absorbed by the skin. Patches are applied daily, typically to the back, abdomen, upper arm or thigh.

InjectionsTestosterone injections, usually in the upper buttock, are typically given every 1-2 weeks. However, there are some long-acting injections that can be administered every 10 weeks.

Buccal TabletIn your mouth, the tablet is applied to the gum, where testosterone is absorbed over a 12-hour period. They are taken twice daily.

PelletsPellets are implanted under the skin near the hip during a surgical procedure by a healthcare provider.

REMEMBER:Regular checkups and age-appropriate screening, including low testosterone, can improve your health and extend your life.

Testosterone therapy should not be used in men with carcinoma of the breast or known or suspected carcinoma of the prostate. Geriatric patients treated with androgens may be at an increased risk for the development ofprostatic hyperplasiaand prostatic carcinoma.

To learn more about Hypogonadism visit the following pages

MedscapeCleveland ClinicMedline PlusWhat Men Should Know About Testosterone

The following professional and patient care organizations are available as resources for further information about low Testosterone and testosterone replacement therapy:

American Academy of Family Healthcare providers (AAFP)11400 Tomahawk Creek ParkwayLeawood, KS 66211913-906-6000www.aafp.org

American Osteopathic Association (AOA)142 E. Ontario St.Chicago, IL 60611-2864800-621-1773www.osteopathic.org

American Association of Clinical Endocrinologists (AACE)1000 Riverside Avenue, Suite 205Jacksonville, FL 32204904-353-7878www.aace.com

American Society for Reproductive Medicine1209 Montgomery HighwayBirmingham, AL 35216205-978-5000www.asrm.org

American Urologic Association (AUA)1000 Corporate BoulevardLinthicum, MD 21090410-689-3700www.auanet.org

The Endocrine Society8401 Connecticut Avenue, Suite 900Chevy Chase, MD 20815301-941-0200www.endo-society.org

The Hormone Foundation8401 Connecticut Avenue, Suite 900Chevy Chase, MD 20815800-HORMONEwww.hormone.org

Sexual Medicine Society of North America, Inc.1111 North Plaza Drive, Suite 550Schaumburg, IL 60173847-517-7225www.smsna.org

Link:
Hypogonadism (Low Testosterone) | Men's Health Resource Center

Recommendation and review posted by Jack Burke

CRISPR Plasmids

DNA plasmids for single guide RNA and/or Cas9 expression

Validated knock-out cell line service using CRISPR technology.

Genome-wide or pathway-specific CRISPR knock-out or activation libraries for screening experiments.

Validated knock-out and knock-in mutagenesis in bacteria and yeast.

CRISPR News

July 6, 2017

For the first time, researchers have been able to detect and characterize the mechanism of action by which the CRISPR complex binds and cleaves DNA using electron microscopy. Scientists at Harvard and Cornell have recently created near-atomic level resolution images of the CRISPR/Cas3 complex, a common CRISPR/Cas subtype, which provide structural data that can improve gene editing accuracy and efficiency.

To solve problems of specificity, we need to understand every step of CRISPR complex formation, states Maofu Liao, a co-author of the study and assistant professor at Harvard. Our study now shows the precise mechanism for how invading DNA is captured by CRISPR, from initial recognition of target DNA and through a process of conformational changes that make DNA accessible for final cleavage by Cas3.

This discovery uncovers a number of novel, overlapping mechanisms which prevent off-target site cleavage. In the CRISPR/Cas3 system, the assembled CRISPR complex first searches for a corresponding protospacer adjacent motif (PAM) sequence, which indicates a possible target site. Researchers discovered that as the CRISPR complex detects the PAM, it also bends DNA at a sharp angle, forcing a small portion to unwind. This allows an 11-nucleotide stretch of the CRISPR guide RNA to bind onto the target DNA, creating a seed bubble. The seed bubble acts as a fail-safe mechanism to check whether target DNA matches the guide RNA. If correctly matched, the bubble is enlarged and the remainder of the guide RNA binds onto the DNA forming an R-loop structure. Only once the full R-loop structure is formed does the Cas enzyme bind and cut the DNA in the non-target DNA strand. This study is the first to reveal the full sequence of events from seed bubble formation to R-loop formation.

Looking for an affordable and easy way to model disease in vivo?Interested in performing a genome-wide screen?Use CRISPR RNA/Cas9 Reagents or CRISPR Plasmids for high efficiency, customizable gene editing.

Xiao, Y. et al. Structure Basis for Directional R-loop Formation and Substrate Handover Mechanisms in Type I CRISPR-Cas System.Cell170, 48-60.e11 (2017).

June 28, 2017

Today, nearly 1 out of every 68 children born is diagnosed with autism spectrum disorder (ASD). Globally the disease is estimated to affect over 25 million people. And prevalence is expected to rise with ASD identifications doubling in the last decade.

ASD describes a variety of neurodevelopmental disorders which are often characterized by deficits in social communication and interaction, and restricted and repetitive behavior. While no specific causes for ASD have yet been found, a number of genetic and environmental risk factors have been identified. Most recently, a new study from Columbia Universitys Mailman School of Public Health, has discovered that prenatal fever increases autism risk by up to 40%.

Researchers monitored over 95,000 children born between 1999 and 2009. Of that population, 15,701 children were identified to have mothers reporting fever conditions during pregnancy. These children were found to have increased risk of ASD by 34%. Risk increase was highest, at 40%, when fever was reported during the second trimester. And ASD risk was increased by over 300% for the children of women reporting three or more fevers after the twelfth week of pregnancy.

Our results suggest a role for gestational maternal infection and innate immune responses to infection in the onset of at least some cases of autism spectrum disorder, states lead researcher, Associate Professor Mady Hornig. Additional studies are ongoing to determine the role of specific infectious agents in the development of ASD.

Hornig, M. et al. Prenatal fever and autism risk. Molecular Psychiatry (2017). doi:10.1038/mp.2017.119

June 22, 2017

Each year almost 200,000 people in the U.S. require emergency medical care for a serious allergic reaction. This number is expected to grow as food allergy incidence has increased by 50% in the last decade.

Allergies are caused from the hypersensitivity of the immune system to allergens in the environment. Recognition of these allergens triggers a T-cell-mediated immune response, producing cytokines which induce chronic inflammation and mucous hypersecretion.

In a recent study at the University of Queensland, Professor Ray Steptoe has been able to de-sensitize T-cells using a novel gene therapy treatment. Dr. Steptoes research team has engineered bone marrow stem cells to express transgenic allergen proteins. This effectively tricks the body into identifying the transgenic allergen as a self-antigen originating from within the body, leading to negative selection of any reacting T-cells. After treatment, the immune system is memory wiped alleviating airway inflammation and hyperreactivity.

Dr. Steptoe states that the eventual goal will be to devise a single-dose injectable therapeutic, which could replace the various short-term treatments that focus on alleviating allergy symptoms. Potential patents would be those individuals who are suffering from potentially lethal allergies or severe asthma.

AL-Kouba, J. et al. Allergen-encoding bone marrow transfer inactivates allergic T cell responses, alleviating airway inflammation. JCI Insight2, (2017).

June 15, 2017

Each year nearly 2 million people in the USA are infected by antibiotic-resistant bacteria. With antibiotic resistance on the rise, scientists have begun to turn to alternative antimicrobial treatments.

At the University of Wisconsin-Madison, scientists are developing a new probiotic "CRISPR pill" that is effective even against drug-resistant threats. Researchers from the lab of Jan-Peter Van Pijkeren have engineered bacteriophages expressing customized CRISPR guide RNA sequences. These CRISPR RNAs hijack the innate bacterial CRISPR immunity system present in infectious bacteria, causing them to self-destruct by creating lethal breaks in their own DNA. The bacteriophages are packaged in pill form in a mixture of probiotics, allowing them to survive the digestive tract until reaching the intestines.

By utilizing the innate immune system present in bacteria, the CRISPR pill bypasses the main mechanisms of antibiotic resistance. In addition, CRISPR pills may be superior to traditional antibiotics, because of their narrow targeting spectrum which can target specific bacterial species and strains. In contrast, broad-spectrum antibiotics kill off both "good" and "bad" bacteria. And overuse of traditional antibiotics has lead to the rising epidemic of antibiotic-resistant infections.

CRISPR and the CRISPR Associated system (Cas) is a powerful gene editing technology. Originally identified and characterized in bacteria, endogenous CRISPR systems act as an RNA-based defense mechanism against invading phage DNA.

CRISPR was adapted for genome editing in 2013 and has since been exploited for its ability to generate targeted double-stranded DNA breaks, which has revolutionized molecular biology protocols.1,2

This guide covers the basics of CRISPR experimental design and will prepare you to embark upon your own genome editing experiment.

Endogenous CRISPR systems fall into three categories type I, II and II. You can read more about these types in Makarova et al.3 Commercial CRISPR genome editing tools are adapted and simplified from endogenous type II systems and have the following components:

When gRNA and Cas9 are expressed together in a cell, a gRNA:Cas9 complex is recruited to the target DNA sequence, which is located immediately upstream of a motif called a protospacer adjacent motif (PAM).4 The PAM motif targeted by most commercial Cas9 enzymes is NGG (any nucleotide followed by two guanines).

Binding of the gRNA to target DNA occurs via complementary base-pairing between the genomic target sequence and the 20-nucleotide spacer on the gRNA. The Cas9 in the gRNA:Cas9 complex then cuts the genomic DNA, inducing a double-stranded break after the PAM sequence. Crucially, Cas9 cannot digest DNA unless bound to the gRNA, thus providing specificity to the system.

The editing process is completed by repairing the break using the endogenous Non-Homologous End Joining (NHEJ) pathway. While this DNA repair system is the most efficient repair pathway it is error prone, sometimes permitting small insertions or deletions, which can result in frameshifts and reduced protein production. An alternative option is to exploit the endogenous Homology Directed Repair (HDR) system by providing the HR template, as mentioned above. This is used when introducing targeted mutations.

Once you have designed and cloned the gRNA and HR templates, you cotransfect the Cas9 plasmid and your gRNA and HR donor vectors into the chosen cell line. Lipid transfection, electroporation or microinjection are all suitable transfection methods.

Optimizing recombination levels may take some trial and error. Choose a robust cell line (e.g., HEK) for troubleshooting. Once your experiment is up and running, you can move onto more expensive and less robust cell lines, if necessary.

Bear in mind that immortalized cell lines are not only cheaper than primary cells, but their recombination pathways are often less stringent. Therefore, you should ideally achieve a high level of recombination efficiency before moving to primary lines.

In the end, efficiency of your CRISPR experiment is part plan, part luck. The interaction between the system components and Cas9 is still not well understood. Fortunately, there are a few ways you can increase your odds:

If you have done everything right but are still experiencing low efficiency, then it is time to experiment. You may have better luck using sense and anti-sense templates. Others have reported better efficiency with asymmetrical arms.5 Be prepared to design a few setups the efficiencies of overlapping designs can vary widely and be ready to experiment to find the best design for your experiments. For more information about CRISPR, check out this free CRISPR handbook.

How to Optimize Your Lentiviral ExperimentsMarch 7, 2017

There are several aspects to consider if you want to optimize your lentiviral experiments. Check out these helpful tips before you embark on the incessant optimization experiments. Here are three common factors that may be affecting your viral titers:

The 293 cell line was derived from embryonic kidney cells and is commonly used for lentivirus production. HEK 293 cells are sensitive to passage number and should be replaced regularly; cells must be healthy and actively dividing. HEK 293Ts, which contain the SV40 T antigen, are more resilient and can be used for six months or longer with no significant reduction in virus titer.

Clumpy cell cultures with lots of senescent cells will not produce good titers. It is worth doing a test transfection on your cells before you try using them for virus production. If your transfection efficiency is low, then there is no point continuing with virus production, you will need to setup a new cell stock.

Remember:

There are a number different commercial and non-commercial transfection reagents available. Chemical reagents such as calcium phosphate and polyethylenimine (PEI) work effectively and are very budget-friendly. For transfection with PEI or a commercial lipid-based reagent, your 293 cells should be 90-95% confluent at the time of transfection.

Remember:

A lentivirus expression typically contains a transfer plasmid and a packaging plasmid. Plasmids are recommended to be cultivated from bacterial strains such as Stbl3, which have reduced frequencies of homologous recombination. Plasmids containing a Gateway cassette with the ccdBgene will require a compatible ccdB viable strain. Make sure after plasmid purification that plasmid quality is high and of a reasonable concentration (over 100ng/L).

When considering packaging plasmids, make sure not to confuse the second and third generation variants. Second generation transfer plasmids require the presence of HIV-1 Tat protein. Third generation transfer plasmids have eliminated Tat from the packaging system, but are still backwards compatible with second generation transfer plasmids.

Transfer plasmids are the most important factor in virus production, and can result in transduction efficiency differences of 10-50x. The length of sequence between the long terminal repeats can directly influence viral titer, and particle yield decreases as sequence length increases. Including multiple promoters within the transfer plasmid can also result in promoter interference, where the promoters adversely affect expression of the others, resulting in lower viral titer.

Fluorescence microscopy and flow cytometry are two methods that can be used to measure transduction efficiency. Remember though that protein expression can influence fluorescence, and weakly expressed proteins can lead to underestimated viral titer. Therefore, promoter should be a key consideration if transduction is assessed using these methods.

Remember:

Researchers uncover novel fat metabolism pathwayFebruary 20, 2017

A new study in Nature Communications discovered a neuropeptide hormone, FLP-7, which is capable of stimulating fat metabolism. This fat metabolism pathway is the first to be discovered which can activate fat burning without affecting food intake or movement.

FLP-7 had previously been identified over 80 years ago as a muscle stimulant, but no links to fat metabolism was ever established. Flashing forward to 2017, scientists at the Scripps Institute identified FLP-7 during a genetic screen as a suppressor of fat loss in C. elegans roundworms. By fluorescently tagging the hormone, researchers were able to track FLP-7 secretions from the brain in response to elevated serotonin levels. This FLP-7 could then be tracked through the circulatory system to the gut, where it activates fat burning.

Modifying serotonin levels results in serious side effects, broadly impacting food intake, movement and reproduction. Amazingly, adjusting levels of FLP-7 does not result in any obvious changes, worms continue to function normally, while just burning more fat. Researchers hope their finding spur additional research into the weight loss effects of FLP-7 mammalian homologs.

Palamiuc et al. A tachykinin-like neuroendocrine signalling axis couples central serotonin action and nutrient sensing with peripheral lipid metabolism.Nature Communications, 2017; 8: 14237 DOI:10.1038/ncomms14237

How does sugar effect health and aging?February 6, 2016

A new study in Cell Reports has linked sugar intake to lifespan. This process occurs through a newly discovered pathway in which sugar permanently reprograms gene expression, maintaining an altered state even if your diet has improved.

Using fruit flies as a model organism, researchers compared life span of flies consuming a 5% and 40% sugar diet. Any flies raised on the 40% sugar diet averaged a 7% shorter life span. Researchers discovered that excess sugar promotes insulin-signaling pathways which lead to the inactivation of FOXO. FOXO is a transcription factor which alters the expression levels of chromatin modifiers. Crucially, the reprogramming of these transcription networks could not be reversed upon a switch to the lower sugar diet. The study improves our understanding of how changes in diet and gene expression can affect the speed of aging.

Dobson et al.Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets.Cell Reports, 2017; 18 (2): 299 DOI:10.1016/j.celrep.2016.12.029

How does vitamin C fight cancer?January 30, 2016

Vitamin C's efficacy in cancer prevention has been hotly debated. But, new research has shown that direct, intravenous delivery of vitamin C can more than double survival rates of pancreatic cancer. By avoiding the digestive tract, scientists have been able to increase vitamin C levels in the blood by 100-500 times. And at these extreme concentrations, vitamin C is able to selectively kill cancer cells.

As Vitamin C breaks down through oxidation hydrogen peroxide is generated. Hydrogen peroxide is capable of forming free radicals which can be damaging to DNA. Interestingly, researchers discovered that tumor cells are much less efficient at removing hydrogen peroxide. Tumor cells were found to be deficient in catalase activity, the primary means of detoxifying hydrogen peroxide. On average, tumor cells were able to only metabolize hydrogen peroxide at half the rate of normal cells. And the addition of vitamin C to these tumor cells resulted in ATP depletion, DNA lesions, and cell growth reduced by more than 50%. Clinical trials pairing both high-dosage, intravenous vitamin C and chemotherapy are now underway and in Phase 2 testing.

Doskey et al.Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy.Redox Biology, 2016; 10: 274 DOI:10.1016/j.redox.2016.10.010

Postdoc vs Industry? Comparing the ReturnsJanuary 23, 2016

A new study published in Nature Biotechnology has found that biomedical postdoctoral opportunities provide diminishing returns in the labor market. Upon graduating, many aspiring postdocs will hope to land a career in tenure track academia, but only 20% of scientists ever manage to attain such a position. The impact from such a decision can be staggeringly high.

Taking a postdoctoral position can cost up to three years worth of lost salary over the first 15 years of a scientist's career. In 2013, the median starting salary for postdocs in academia was $44,724, compared to $73,662 for postdocs in industry. The academic experience accrued does not improve salary potential either, as scientists switching to industry average salaries equivalent to new, entry-level employees. Overall, academics will average $12,002 lower than though who leave the field.

But current graduates should stay informed of their options, and measure the chance of landing a tenure-track position against the potential financial ramifications.

Kahn and Ginther, 2017. The impact of postdoctoral training on early careers in biomedicine.Nature Biotechnology 2017; 35 (1): 90 DOI: 10.1038/nbt.3766

New mechanism for cancer metastasis discoveredJanuary 16, 2016

Cell biologists at Mount Sinai have identified a combination of changes to oncogenic and tumor suppressor genes which allow for early dissemination of cancer cells before a primary tumor forms. These cells first migrate before attaining additional mutations which lead to uncontrolled cell proliferation. But, a majority of the disseminated cancer cells will remain quiescent. And due to their non-proliferative nature, these cells form a reservoir resistant to chemotherapy and other conventional cancer treatments.

This early dissemination is a result of the activation of the p38 and HER2 pathways. Pathway activation leads to a cell type transition from epithelial to mesenchymal cells, which promotes cell migration. This process occurs normally in development during the formation of mammary and pancreatic ducts. But, the over-activation of both pathways during oncogenesis instead allows cancer cells to migrate into the bloodstream and metastasize instead.

Harper et al., 2016. Mechanism of early dissemination and metastasis in Her2 mammary cancer.Nature DOI: 10.1038/nature20609

Hosseimi et al., 2016. Early dissemination seeds metastasis in breast cancer.Nature DOI: 10.1038/nature20785

Mechanism behind Zika microcephaly revealedJanuary 9, 2016

Zika infection during fetal development has been associated with microcephaly and other birth defects. New analysis of Zika viral proteins has identified the mechanism by which the virus damages brain cells.

Cell biologists at Boston Children's Hospital have identified the viral enzyme NS3 as the main culprit in Zika-associated neural degeneration. NS3 functions in the cleavage and processing of other Zika viral proteins. But, NS3 also is capable of interacting with and damaging centrioles, which are required for spindle assembly and cell proliferation. These findings are corroborated by genetic studies which have identified an association between centriole stability and microcephaly.

NS3 may prove to be an important drug target for against Zika-related illnesses moving forward. NS3 inhibitors commonly used to protect against dengue, a related virus, were shown to be successful in preventing NS3 binding to centrioles.

Saey, Tina.Cell biologists learn how Zika kills brain cells, devise schemes to stop it ScienceNews ScienceNews, 13 Dec 2016

How Did Mammary Glands EvolveJanuary 2, 2016

Researchers have recently discovered a new network of genes and enhancers responsible for coordinating the formation of mammary glands. Interestingly, this regulatory network functions by hijacking existing limb development processes.

Hox genes are a subset of homeotic genes which control embryonic development and patterning. Hox genes have been shown to regulate limb, head, thoracic, abdomen, and mammary gland formation.

To better understand how some of these body structures evolved, geneticists at the University of Geneva and the Swiss Federal Institute of Technology in Lusanne screened for Hox gene activating sequences in the genome. One of the enhancer sequences identified, MBRE, was found to be responsible for activating Hoxd9, a gene required for mammary gland development. Interestingly, MBRE is conserved only in placental and marsupial mammals, and missing in egg laying mammals, such as the platypus.

But MBRE regulatory network is found to function in all tissues, indicating that the network was present prior to mammary gland evolution. The researchers propose that Hoxd gene regulation in mammary glands evolved by co-opting existing regulatory networks in other body structures.

CRISPR Gene Editing Tested in Humans for the First TimeDecember 12, 2016

More:
CRISPR News - GenScript

Recommendation and review posted by simmons

OxandroloneClinical dataTrade namesOxandrin, Anavar, othersSynonymsVar; CB-8075; NSC-67068; SC-11585; Protivar; 17-Methyl-2-oxa-4,5-dihydrotestosterone; 17-Methyl-2-oxa-DHT; 17-Methyl-2-oxa-5-androstan-17-ol-3-oneAHFS/Drugs.comMonographMedlinePlusa604024PregnancycategoryRoutes ofadministrationBy mouthDrug classAndrogen; Anabolic steroidATC codeLegal statusLegal statusPharmacokinetic dataBioavailability97%[2]Protein binding9497%[2]MetabolismKidneys (primarily), liver[1][2]Elimination half-lifeAdults: 9.410.4 hours[2][3]Elderly: 13.3 hours[3]ExcretionUrine: 28% (unchanged)[3]Feces: 3%[3]Identifiers

O=C3OC[C@@]2([C@H]1CC[C@@]4(C)[C@H]([C@@H]1CC[C@H]2C3)CC[C@@]4(O)C)C

Oxandrolone, sold under the brand names Oxandrin and Anavar among others, is an androgen and anabolic steroid (AAS) medication which is used to help promote weight gain in various situations, to help offset protein catabolism caused by long-term corticosteroid therapy, to support recovery from severe burns, to treat bone pain associated with osteoporosis, to aid in the development of girls with Turner syndrome, and for other indications.[4][5][6] It is taken by mouth.[4]

Side effects of oxandrolone include symptoms of masculinization like acne, increased hair growth, voice changes, and increased sexual desire.[4] Uniquely among most AAS that are active by mouth, it seems to have little risk of liver damage.[4][7] The drug is a synthetic androgen and anabolic steroid and hence is an agonist of the androgen receptor (AR), the biological target of androgens like testosterone and dihydrotestosterone (DHT).[4][8] It has strong anabolic effects and weak androgenic effects, which give it a mild side effect profile and make it especially suitable for use in women.[4]

Oxandrolone was first described in 1962 and was introduced for medical use in 1964.[4] It is used mostly in the United States.[4][9] In addition to its medical use, oxandrolone is used to improve physique and performance.[4][10] The drug is a controlled substance in many countries and so non-medical use is generally illicit.[4][11][12][13]

Oxandrolone has been researched and prescribed as a treatment for a wide variety of conditions. It is FDA-approved for treating bone pain associated with osteoporosis, aiding weight gain following surgery or physical trauma, during chronic infection, or in the context of unexplained weight loss, and counteracting the catabolic effect of long-term corticosteroid therapy.[14][15] As of 2016[update], it is often prescribed off-label to quicken recovery from severe burns, aid the development of girls with Turner syndrome, and counteract HIV/AIDS-induced wasting. Oxandrolone improves both short-term and long-term outcomes in people recovering from severe burns and is well-established as a safe treatment for this indication.[5][6] It is also used in the treatment of idiopathic short stature, anemia, hereditary angioedema, alcoholic hepatitis, and hypogonadism.[16][17]

Medical research has established the effectiveness of oxandrolone in aiding the development of girls with Turner syndrome. Although oxandrolone has long been used to accelerate growth in children with idiopathic short stature, it is unlikely to increase adult height, and in some cases may even decrease it. Oxandrolone has, therefore, largely been replaced by growth hormone for this use.[18] Children with idiopathic short stature or Turner syndrome are given doses of oxandrolone far smaller than those given to people with burns in order to minimize the likelihood of virilization and premature maturation.[18][19]

Many bodybuilders and athletes use oxandrolone for its muscle-building effects.[4] It is much more anabolic than androgenic, so women and those seeking less intense steroid regimens use it particularly often.[4] Many also value oxandrolone's low hepatotoxicity relative to most other orally active AAS.[4]

Like other AAS, oxandrolone may worsen hypercalcemia by increasing osteolytic bone resorption.[14] When taken by pregnant women, oxandrolone may have unintended effects such as masculinization on the fetus.[14]

Women who are administered oxandrolone may experience virilization, irreversible development of masculine features such as voice deepening, hirsutism, menstruation abnormalities, male-pattern hair loss, and clitoral enlargement.[18][14][19] Oxandrolone may disrupt growth in children, reducing their adult height.[20][bettersourceneeded] Because of these side effects, doses given to women and children are minimized and people are usually monitored for virilization and growth abnormalities.[18][19] Like other androgens, oxandrolone can cause or worsen acne and priapism (unwanted or prolonged erections).[14][20] Oxandrolone can also reduce males' fertility, another side effect common among androgens.[20] In an attempt to compensate for the exogenous increase in androgens, the body may reduce testosterone production via testicular atrophy and inhibition of gonadotropic activity.[14]

Unlike some AAS, oxandrolone does not generally cause gynecomastia because it is not aromatized into estrogenic metabolites.[21] However, although no reports of gynecomastia were made in spite of widespread use, oxandrolone was reported in a publication in 1991 to have been associated with 33cases of gynecomastia in adolescent boys treated with it for short stature.[22][23] The gynecomastia developed during oxandrolone therapy in 19 of the boys and after the therapy was completed in 14 of the boys, and 10 of the boys had transient gynecomastia, while 23 had persistent gynecomastia that necessitated mastectomy.[22][23] Though transient gynecomastia is a natural and common occurrence in pubertal boys, the gynecomastia associated with oxandrolone was of a late/delayed onset and was persistent in a high percentage of the cases.[22][23] As such, the researchers stated, "although oxandrolone cannot be implicated as stimulatory [in] gynecomastia", a possible relationship should be considered in clinicians using oxandrolone in adolescents for growth stimulation.[22][23]

Uniquely among 17-alkylated AAS, oxandrolone shows little to no hepatotoxicity, even at high doses.[7][unreliable medical source?][24] No cases of severe hepatotoxicity have been singularly attributed to oxandrolone.[24] However, elevated liver enzymes have been observed in some people, particularly with high doses and/or prolonged treatment, although they return to normal ranges following discontinuation.[24] In any case, oxandrolone may be among the safest 17-alkylated AAS in terms of hepatotoxicity.[7][unreliable medical source?]

Oxandrolone greatly increases warfarin's blood-thinning effect, sometimes dangerously so.[25] In April 2004, Savient Pharmaceuticals published a safety alert through the FDA warning healthcare professionals of this.[26] Oxandrolone can also inhibit the metabolism of oral hypoglycemic agents.[14] It may worsen edema when taken alongside corticosteroids or adrenocorticotropic hormone.[14]

Like other AAS, oxandrolone is an agonist of the androgen receptor (AR), similarly to androgens like testosterone and DHT.[4] This increases protein synthesis, which increases muscle growth, lean body mass, and bone mineral density.[6]

Compared to testosterone and many other AAS, oxandrolone is less androgenic relative to its strength as an anabolic.[4][27] Oxandrolone has about 322 to 633% of the anabolic potency and 24% of the androgenic potency of methyltestosterone.[4] Similarly, oxandrolone has as much as 6times the anabolic potency of testosterone and has significantly reduced androgenic potency in comparison.[4] The reduced ratio of anabolic to androgenic activity of oxandrolone often motivates its medical use in children and women because less androgenic effect implies less risk of virilization.[4] The bodybuilding community also considers this fact when choosing between AAS.[4]

As oxandrolone is already 5-reduced, it is not a substrate for 5-reductase and hence is not potentiated in androgenic tissues such as the skin, hair follicles, and prostate gland.[4] This is involved in its reduced ratio of anabolic to androgenic activity.[4] Due to the substitution of one of the carbon atoms with an oxygen atom at the C2 position in the A ring, oxandrolone is resistant to inactivation by 3-hydroxysteroid dehydrogenase in skeletal muscle.[4] This is in contrast to DHT and is thought to underlie the preserved anabolic potency with oxandrolone.[4] Because it is 5-reduced, oxandrolone is not a substrate for aromatase and hence cannot be aromatized into metabolites with estrogenic activity.[4] Oxandrolone similarly possesses no progestogenic activity.[4]

Oxandrolone is, uniquely, far less hepatotoxic than other 17-alkylated AAS, which may be due to differences in metabolism.[24][4][1][3]

The oral bioavailability of oxandrolone is 97%.[2] Its plasma protein binding is 94 to 97%.[2] The drug is metabolized primarily by the kidneys and to a lesser extent by the liver.[1][2] Oxandrolone is the only AAS that is not primarily or extensively metabolized by the liver, and this is thought to be related to its diminished hepatotoxicity relative to other AAS.[1][3] Its elimination half-life is reported as 9.4 to 10.4hours but is extended to 13.3hours in the elderly.[2][3] Approximately 28% of an oral dose of oxandrolone is eliminated unchanged in the urine and 3% is excreted in the feces.[3]

Oxandrolone is a synthetic androstane steroid and a 17-alkylated derivative of DHT.[28][29][4] It is also known as 2-oxa-17-methyl-5-dihydrotestosterone (2-oxa-17-methyl-DHT) or as 2-oxa-17-methyl-5-androstan-17-ol-3-one, and is DHT with a methyl group at the C17 position and the C2 carbon replaced with an oxygen atom.[28][29][4] Closely related AAS include the marketed AAS mestanolone (17-methyl-DHT), oxymetholone (2-hydroxymethylene-17-methyl-DHT), and stanozolol (a 2,3-pyrazole A ring-fused derivative of 17-methyl-DHT) and the never-marketed/designer AAS desoxymethyltestosterone (3-deketo-17-methyl-2-DHT), methasterone (2,17-dimethyl-DHT), methyl-1-testosterone (17-methyl-1-DHT), and methylstenbolone (2,17-dimethyl-1-DHT).[28][29][4]

Oxandrolone was first made by Raphael Pappo and Christopher J. Jung while at Searle Laboratories (now part of Pfizer). The researchers first described the drug in 1962.[4][30][31] They were immediately interested in oxandrolone's very weak androgenic effects relative to its anabolic effects.[30][4] It was introduced as a pharmaceutical drug in the United States in 1964.[4]

The drug was prescribed to promote muscle regrowth in disorders which cause involuntary weight loss, and is used as part of treatment for HIV/AIDS.[4] It had also been shown to be partially successful in treating cases of osteoporosis.[4] However, in part due to bad publicity from its illicit use by bodybuilders, production of Anavar was discontinued by Searle Laboratories in 1989.[4] It was picked up by Bio-Technology General Corporation, which changed its name to Savient Pharmaceuticals, which following successful clinical trials in 1995, released it under the brand name Oxandrin.[4] BTG subsequently won approvals for orphan drug status by the Food and Drug Administration for treating alcoholic hepatitis, Turner syndrome, and HIV-induced weight loss.[4] It is also indicated as an offset to protein catabolism caused by long-term administration of corticosteroids.[4]

Oxandrolone is the generic name of the drug and its INN, USAN, USP, BAN, DCF, DCIT, and JAN, while ossandrolone is or was formerly the DCIT.[28][29][32][9][33]

The original brand name of oxandrolone was Anavar, which was marketed in the United States and the Netherlands.[4][34] This product was eventually discontinued and replaced in the United States with a new product named Oxandrin, which is the sole remaining brand name for oxandrolone in the United States.[4][35] Oxandrolone has also been sold under the brand names Antitriol (Spain), Anatrophill (France), Lipidex (Brazil), Lonavar (Argentina, Australia, Italy), Protivar, and Vasorome (Japan) among others.[4][29][34][36] Additional brand names exist for products that are manufactured for the steroid black market.[4]

Among those using oxandrolone for non-medical purposes, it is often referred to colloquially as "Var", a shortened form of the brand name Anavar.[37][38][39][self-published source]

Oxandrolone is one of the few AAS that remains available for medical use in the United States.[35] The others (as of November 2017) are testosterone, testosterone cypionate, testosterone enanthate, testosterone undecanoate, methyltestosterone, fluoxymesterone, nandrolone decanoate, and oxymetholone.[35]

Outside of the United States, the availability of oxandrolone is quite limited.[4][9] With the exception of Moldova, it is no longer available in Europe.[4] Oxandrolone is available in some less regulated markets in Asia such as Malaysia.[4] It is also available in Mexico.[4] Historically, oxandrolone has been marketed in Argentina, Australia, Brazil, France, Italy, Japan, and Spain, but it appears to no longer be available in these countries.[4][29][34][9]

In the United States, oxandrolone is categorized as a Schedule III controlled substance under the Controlled Substances Act along with many other AAS.[11] It is a Schedule IV controlled substance in Canada,[12] and a Schedule 4 Controlled Drug in the United Kingdom.[13]

Oxandrolone is sometimes used as a doping agent in sports. There are known cases of doping in sports with oxandrolone by professional athletes.

Read more:
Oxandrolone - Wikipedia

Recommendation and review posted by sam

Get your Stem Cell Treatment in India with Dheeraj Bojwani Consultants

Stem Cell treatment is an intricate process. Stem Cell transplant patients need utmost care with respect to both emotionally and physically. Dheeraj Bojwani Consultants is a prominent medical tourism company in India making world-class medical facilities from best surgeons and hospitals accessible for international patients looking for budget-friendly treatment abroad.

Mrs. Marilyn Obiora - Nigeria Stem Cell Therapy For her Daughter in India

Hi, my name is Mrs. Marilyn Obiora, and I am from Nigeria. I came to India for my daughter's Stem Cell Therapy in India. My daughter had her first stroke in 2011. She couldn't sit, talk and had lost control of her neck. We could not find suitable help for her condition and searched for treatment in India.

We sent a query to the dheerajbojwani.com and received fast reply. Within no time we were in India for my daughter's treatment. We are very pleased with the treatment offered and there has been serious improvement in her condition in just two weeks. Thanks to the Dheeraj Bojwani Consultants, my daughter is regaining proper body functions and recuperating well.

Medical science has come a long way since its practice began thousands of years ago. Scientists are finding superior and more resourceful ways to cure diseases of different organs. Stem cells are undifferentiated parent cells that can transform into specialized cell types, divide further and produce more stem cells of the same group. Stem Cell therapy is performed to prevent or treat a health condition. Stem Cell Treatment is a reproductive therapy where nourishing tissues reinstate damaged tissues for relief from incurable diseases. Stem cell treatment is one of the approaches with a potential to heal a wide range of diseases in the near future. Science has always provided ground-breaking answers to obdurate health conditions, but the latest medical miracle that the medical fraternity has gifted to mankind is the Stem Cell Therapy.

Stem cell therapy is an array of techniques intended to replace cells damaged or destroyed by disease with healthy functioning ones. Even though the techniques are relatively new, their applications and advantages are broad and surprising the medical world with every new research. Stem cells are obtained from bone marrow or human umbilical cord. They are also known as the fundamental cells of our body and have the power to develop into any type of tissue cell in the body. Stem cell treatment is based on the principle that the cells move to the site of injury and transform themselves to form new tissue cells to replace the damaged ones. They have the capacity to proliferate and renew themselves indefinitely and can form mature muscle cells, nerve cells, and blood cells. In this type of therapy, they are derived from the body, kept under artificial conditions where they mature into the type of cells that are required to heal a certain part of the body or disease.

Stem cells are being studied and used to treat different types of cancers, disorders related to the blood, immune disorders, and metabolic disorders. Some other diseases and health conditions that may be healed using stem cell treatment are,

Recently, a team of researchers successfully secured the peripheral nerves in the upper arms of a patient suffering peripheral nerve damage, by using skin-derived stem cells (SDSCs) and a previously developed collagen tube, premeditated to successfully bridge gaps in injured nerves.

A research has found potential in bone marrow stem cell therapy to treat TB. Patients injected with new mesenchymal stromal cells derived from their own bone marrow showed positive response against the TB bacteria. The therapy also didnt show any serious adverse effects.

Stem cells are also used to treat hair loss. A small amount of fat is taken from the waist area of the patient by a mini-liposuction process. This fat contains dormant stem cells, and is then spun to separate the stem cells from the fat. An activation solution is added to the cells, and may be multiplied in number, depending on the size of the bald area. Once activated, the solution is washed off so that only cells remain. Now, the stem cells are injected into the scalp. One can find some hair growth in about two to four weeks.

Damaged cones in retinas can be regenerated and eyesight restored through stem cell. Stem cell therapy could regenerate damaged cones in people, especially in the cone-rich regions of the retina that provide daytime/color vision.

Kidney transplants have become more common and easier thanks stem cell therapy. Normally patients who undergo organ transplants need a lifetime of costly anti-rejection drugs but the new procedure may negate this need, with organ donors stem cells. Unless there is a perfect match donor, patients have to wait long for an organ transplant. Though still in early stages, the stem cell research is being considered as a potential player in the field of transplantation.

Transplanted stem cells serve as migratory signals for the brain's own neurogenic cells, guiding the new host cells towards the injured brain tissue. Stem cells have the potential to give rise to many different cell types that carry out different functions. While the stem cells in adult bone marrow tend to develop into the cells that make up the organ system from which they originated. These multipotent stem cells can be manipulated to take up the characteristics of neural cells.

Experts are using Stem cell Transplant to treat the symptoms of spinal cord injury by transplantation of cells directly into the gray matter of the patients spinal cord. Expectedly, the cells will integrate into the patients own neural tissue and create new circuitry to help transmit nerve signals to muscles. The transplanted cells may also promote reorganization of the spinal cord segmental circuitry, possibly leading to improved motor function.

Stem cells are capable of differentiating into a variety of different cell types, and if the architecture of damaged tendon is restored, it would improve the management of patients with these injuries significantly.

A promising benefit of stem cell therapy is its potential for cardiac tissue regeneration to reverse tissue loss underlying the development of heart failure after cardiac injury. Possible mechanisms of recovery include generation of heart muscle cells, stimulation of new blood vessels growth, secretion of growth factors.

It is a complex and multifarious procedure, with several risks and complications involved and is thus recommended to a few patients when other treatments have failed. Stem Cell therapy is recommended when other treatments fail to give positive results. The best candidates for Stem cell Treatment are those in good health and have stem cells available from a sibling, or any other family member.

India has been recognized as the new medical destination for Stem Cell therapies. Hundreds of international patients from around the world visit to India for high quality medical care at par with developed nations like the US, UK, at the most affordable costs. The Hospitals in India have the most extensive diagnostic and imaging facilities including Asias most advanced MRI and CT technology. India provides services of the most leading doctors and Stem Cell Therapy professionals at reasonable cost budget in the following cities

India offers outstanding Stem Cell Treatment at rates far below that prevailing in USA or other Western countries. Even with travel expenses taken into account, the comprehensive medical tourism packages still provide a savings measured in the thousands of dollars for major procedures. A cost comparison can give you the exact idea about the difference:

There are many reasons for India becoming a popular medical tourism spot is the low cost stem cell treatment in the area. When in contrast to the first world countries like, US and UK, medical care in India costs as much as 60-90% lesser, that makes it a great option for the citizens of those countries to opt for stem cell treatment in India because of availability of quality healthcare in India, affordable prices strategic connectivity, food, zero language barrier and many other reasons.

The maximum number of patients for Stem Cell Treatment comes from Nigeria, Kenya, Ethiopia, USA, UK, Australia, Saudi Arabia, UAE, Uzbekistan, Bangladesh

Below are the downloadable links that will help you to plan your medical trip to India in a more organized and better way. Attached word and pdf files gives information that will help you to know India more and make your trip to India easy and memorable one.

Back

Read more from the original source:
Stem Cell Treatment/Therapy COST in India| DheerajBojwani.Com

Recommendation and review posted by simmons

Brief Summary:

This is a phase II, randomized, placebo-controlled clinical trial designed to assess feasibility, safety, and effect of autologous bone marrow-derived mesenchymal stem cells (MSCs) and c-kit+ cardiac stem cells (CSCs) both alone and in combination (Combo), compared to placebo (cell-free Plasmalyte-A medium) as well as each other, administered by transendocardial injection in subjects with ischemic cardiomyopathy.

This is a randomized, placebo-controlled clinical trial designed to evaluate the feasibility, safety, and effect of Combo, MSCs alone, and CSCs alone compared with placebo as well as each other in subjects with heart failure of ischemic etiology. Following a successful lead-in phase, a total of one hundred forty-four (144) subjects will be randomized (1:1:1:1) to receive Combo, MSCs, CSCs, or placebo. After randomization, baseline imaging, relevant harvest procedures, and study product injection, subjects will be followed up at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months post study product injection. All subjects will receive study product injection (cells or placebo) using the NOGA XP Mapping and Navigation System. Subjects will have delayed-enhanced magnetic resonance imaging (DEMRI) scans to assess scar size and LV function and structure at baseline and at 6 and 12 months post study product administration. All endpoints will be assessed at the 6 and 12 month visits which will occur 180 30 days and 365 30 days respectively from the day of study product injection (Day 0). For the purpose of the endpoint analysis and safety evaluations, the Investigators will utilize an "intention-to-treat" study population, however an as treated analysis will also be conducted.

Continue reading here:
Combination of Mesenchymal and C-kit+ Cardiac Stem Cells ...

Recommendation and review posted by Rebecca Evans

There is currently ~1 week time till shipment.

Due to the overwhelming number of emails we will not respond to emails asking when your item will be shipped. Understand we are doing our best to get it to you.

Comes with an example experiment that teaches you many molecular biology and gene engineering techniques.

Want to really know what this whole CRISPR thing is about? Why it could revolutionize genetic engineering? This kit includes everything you need to make precision genome edits in bacteria at home including Cas9, tracrRNA, crRNA and Template DNA template for an example experiment.

Includes example experiment to make a genome mutation(K43T) to the rpsL gene changing the 43rd amino acid, a Lysine(K) to a Threonine(T) thereby allowing the bacteria to survive on Strep media which would normal prevent its growth.

Kit contains enough materials for around 5 experiments or more

Protocol For Experiment

You can find the plasmid DNA sequences

Cas9 Plasmid

gRNA Plasmid

Some items in this kit need to be stored in a fridge and a freezer upon you receiving them.

See the rest here:
DIY CRISPR Kit - The ODIN

Recommendation and review posted by Rebecca Evans

> Dr Geoffrey McCowage, Cancer Gene Therapy Group Leader

Geoffisa Paediatric Oncologist at The Children's Hospital at Westmead and a member of Sydney Cell and Gene Therapy (SCGT). He is a Principal Investigator for clinical trialswithin the Children's Oncology Group. He has a particular clinical interest in neuro-oncology and sarcomas of bone and soft tissue. Dr McCowage leads the clinicaland translational researchof the Cancer Gene Therapy group.

> Dr Belinda Kramer,Cancer Gene Therapy Group Co-Leader, email: belinda.kramer@health.nsw.gov.au

Belinda is a senior research scientist and leadslaboratory research within the Cancer Gene Therapy Group. She is also a member of Sydney Cell and Gene Therapy (SCGT) and highly experienced in genetransfer techniquesand cell therapies.

> Dr Kenneth Hsu, Senior Post-doctoral Research Officer, Cancer Gene Therapy Group Co-Leader, email: kenneth.hsu@health.nsw.gov.au

Ken is an experienced post-doctoral scientist working on the development of novel vectors for gene modification of T cells to target tumours and the development of clinically applicable T cell manufacturing methodology for the project.

> Other Research Team Members

See original here:
The Cancer Gene Therapy Research Team | Kids Research

Recommendation and review posted by sam

Although there are key players in markets like the U.S., Australia, and the EU, Japan continues to accelerates its position as a hub for induced pluripotent stem cell (iPS cell) therapy with generous funding, acquisitions, and strategic partnerships.

Pluripotent stem cells are cells that are capable of developing into any type of cell or tissue in the human body. These cells have the capability to replicate and help in repairing damaged tissues within the body. In 2006, the Japanese scientist Shinya Yamanaka demonstrated that an ordinary cell can be turned into a pluripotent cell by genetic modification. These genetically reprogrammed cells are known as induced pluripotent cells, also called iPS cells or iPSCs.

An induced pluripotent stem cell (iPS cell) is a type of pluripotent stem cell that has the capacity to divide indefinitely and create any cell found within the three germ layers of an organism. These layers include the ectoderm (cells giving rise to the skin and nervous system), endoderm (cells forming gastrointestinal and respiratory tracts, endocrine gland, liver, and pancreas), and mesoderm (cells forming bones, cartilage, most of the circulatory system, muscles, connective tissues, and other related tissues.).

iPS cells have significant potential for therapeutic applications. For autologous applications, the cells are extracted from the patients own body, making them genetically identical to the patient and eliminating the issues associated with tissue matching and tissue rejection.

iPS cells have the potential to be used to treat a wide range of diseases, including diabetes, heart diseases, autoimmune diseases, and neural complications, such as Parkinsons disease, Alzheimers disease.

Over the past few years, Japan has accelerated its position as a hub for regenerative medicine research, largely driven by support from Prime Minister Shinzo Abe who has identified regenerative medicine and cellular therapy as key to the Japans strategy to drive economic growth.

The Prime Minister has encouraged a growing range of collaborations between private industry and academic partners through an innovative legal framework approved last fall.

He has also initiated campaigns to drive technological advances in drugs and devices by connecting private companies with public funding sources. The result has been to drive progress in both basic and applied research involving induced pluripotent stem cells (iPS cells) and related stem cell technologies.

2013 was a landmark year in Japan, because it saw the first cellular therapy involving transplant of iPS cells into humans initiated at the RIKEN Center in Kobe, Japan.[1]Led by Masayo Takahashi of theRIKEN Center for Developmental Biology (CDB).Dr. Takahashi and her team wereinvestigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration.

To speed things along, RIKEN did not seek permission for a clinical trial involving iPS cells, but instead applied for a type of pretrial clinical research allowed under Japanese regulations.The RIKEN Center is Japans largest, most comprehensive research institution, backed by both Japans Health Ministry and government.

This pretrial clinical research allowed the RIKEN research team to test the use of iPS cells for the treatment of wet-type age-related macular degeneration (AMD) on a very small scale, in only a handful of patients.Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them.

However, in June 2016 RIKEN Institute announced that it would be resuming the clinical study involving the use of iPSC-derived cellsin humans.According to theJapan Times, this second attempt at the clinical studyis using allogeneic rather than autologous iPSC-derived cells, because of the greater cost and time efficiencies.

Specifically,the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka.

Japan has a unique affection for iPS cells, as the cells were originally discovered by the Japanese scientist, Shinya Yamanaka of Kyoto University. Mr. Yamanaka was awarded the Nobel Prize in Physiology or Medicine for 2012, an honor shared jointly with John Gurdon, for the discovery that mature cells can be reprogrammed to become pluripotent.

In addition, Japans Education Ministry said its planning to spend 110 billion yen ($1.13 billion) on induced pluripotent stem cell research during the next 10 years, and the Japanese parliament has been discussing bills that would speed the approval process and ensure the safety of such treatments.[3]

In April, Japanese parliament even passed a law calling for Japan to make regenerative medical treatments like iPSC technology available for its citizens ahead of the rest of the world.[4] If those forces were not enough, Masayo Takahashi of the RIKEN Center for Developmental Biology in Kobe, Japan, who is heading the worlds first clinical research using iPSCs in humans, was also chosen by the journal Natureas one of five scientists to watch in 2014.[5]

Clearly, Japan is the global leader in iPS cell technologies and therapies. However, progress with stem cells has not been without setbacks within Japan, including a recent scandal at the RIKEN Institute that involved falsely manipulated research findings and a hold on the first clinical trial involving transplant of an iPS cell product into humans.

Nonetheless, Japan has emerged from these troubles to become the most liberalized nation pursuing the development of iPS cell products and services.

iPS cells represent one of the most promising advances within the field of stem cell research, because of their diverse ability to differentiate into any of the approximately 200 cell types that compose the human body.

Even though there is growing evidence to support the safety of iPS cells within cell therapy applications,some people remain concerned that patients who receive implants of iPS derived cells might be at risk of cancer, as genetic manipulation is required to create the cell type.

In a world-first, Cynata Therapeutics (ASX:CYP) received approval in September 2016 to launch a clinical trial in the UK with the worlds first first formal clinical trial of an allogeneic iPSC-derived cell product, which it calls CYP-001.The study involves centers in both the UK and Australia.

In this landmark trial, the Australian regenerative medicine company is testing an iPS cell-derived mesenchymal stem cell (MSC) product for the treatment of Graft-vs-Host-Disease (GvHD).Not surprisingly, the Japanese conglomerate Fujifilm is also involved with this historic trial.

Headquartered in Tokyo, Fujifilm is one of the largest players in regenerative medicine field and has invested significantly into stem cells through their acquisition of Cellular Dynamics International (CDI). Additionally, Fujifilm has invested in Japan Tissue Engineering Co. Ltd. (J-Tec), giving it a broad base in regenerative medicine across multiple therapeutic areas.

For a young company like Cynata, having validation from an industry giant like Fujifilm is a huge boost. As stated by Cynata CEO, Dr. Ross Macdonald, The decision by Fujifilm confirms that our technology is very exciting in their eyes. It is a useful yardstick for other investors as well. Of course, the effect of the relationship with Fujifilm on our balance sheet is also important.

If Fujifilm exercises their option to license Cynatas GvHD product, then the costs of the product and commercialization will become the responsibility of Fujifilm. Cynata would also receive milestone payments from Fujifilm of approximately $60M AUS and a double-digit royalty payment.

Cynata was also the first to scale-up manufacture of an allogeneic cGMP iPS celll line. It sourced the cell line from Cellular Dynamics International (CDI) when CDI was still an independent company listed on NASDAQ. In April 2015, CDI was subsequently acquired by Fujifilm, who as mentioned, is a major shareholder in Cynata and its strategic partner for GvHD.

Although Cynata is showing promising early-stage data from its GvHD trial, methods for commercializing iPS cells are still being explored and clinical studies investigating iPS cells remain extremely low in number.

Footnotes[1] Dvorak, K. (2014).Japan Makes Advance on Stem-Cell Therapy [Online]. Available at: http://online.wsj.com/news/articles/SB10001424127887323689204578571363010820642. Web. 14 Apr. 2015.[2] Note: In the United States, some patients have been treated with retina cells derived from embryonic stem cells (ESCs) to treat macular degeneration. There was a successful patient safety test for this stem cell treatment last year that was conducted at the Jules Stein Eye Institute in Los Angeles. The ESC-derived cells used for this study were developed by Advanced Cell Technology, Inc, a company located in Marlborough, Massachusetts.[3] Dvorak, K. (2014).Japan Makes Advance on Stem-Cell Therapy [Online]. Available at: http://online.wsj.com/news/articles/SB10001424127887323689204578571363010820642. Web. 8 Apr. 2015.[4] Ibid.[5] Riken.jp. (2014).RIKEN researcher chosen as one of five scientists to watch in 2014 | RIKEN [Online]. Available at: http://www.riken.jp/en/pr/topics/2014/20140107_1/. Web. 14 Apr. 2015.

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iPS Cell Therapy: Is Japan the Market Leader?

Recommendation and review posted by simmons

Human cells resist gene editing by turning on defenses against cancer, ceasing reproduction and sometimes dying, two teams of scientists have found.

The findings, reported in the journal Nature Medicine, at first appeared to cast doubt on the viability of the most widely used form of gene editing, known as Crispr-Cas9 or simply Crispr, sending the stocks of some biotech companies into decline on Monday.

Crispr Therapeutics fell by 13 percent shortly after the scientists announcement. Intellia Therapeutics dipped, too, as did Editas Medicine. All three are developing medical treatments based on Crispr.

But the scientists who published the research say that Crispr remains a promising technology, if a bit more difficult than had been known.

The reactions have been exaggerated, said Jussi Taipale, a biochemist at the University of Cambridge and an author of one of two papers published Monday. The findings underscore the need for more research into the safety of Crispr, he said, but they dont spell its doom.

This is not something that should stop research on Crispr therapies, he said. I think its almost the other way we should put more effort into such things.

Crispr has stirred strong feelings ever since it came to light as a gene-editing technology five years ago. Already, its a mainstay in the scientific tool kit.

The possibilities have led to speculations about altering the human race and bringing extinct species back to life. Crisprs pioneers have already won a slew of prizes, and titanic battles over patent rights to the technology have begun.

To edit genes with Crispr, scientists craft molecules that enter the nucleus of a cell. They zero in on a particular stretch of DNA and slice it out.

The cell then repairs the two loose ends. If scientists add another piece of DNA, the cell may stitch it into the place where the excised gene once sat.

Recently, Dr. Taipale and his colleagues set out to study cancer. They used Crispr to cut out genes from cancer cells to see which were essential to cancers aggressive growth.

For comparison, they also tried to remove genes from ordinary cells in this case, a line of cells that originally came from a human retina. But while it was easy to cut genes from the cancer cells, the scientists did not succeed with the retinal cells.

Such failure isnt unusual in the world of gene editing. But Dr. Taipale and his colleagues decided to spend some time to figure out why exactly they were failing.

They soon discovered that one gene, p53, was largely responsible for preventing Crispr from working.

p53 normally protects against cancer by preventing mutations from accumulating in cellular DNA. Mutations may arise when a cell tries to fix a break in its DNA strand. The process isnt perfect, and the repair may be faulty, resulting in a mutation.

When cells sense that the strand has broken, the p53 gene may swing into action. It can stop a cell from making a new copy of its genes. Then the cell may simply stop multiplying, or it may die. This helps protect the body against cancer.

If a cell gets a mutation in the p53 gene itself, however, the cell loses the ability to police itself for faulty DNA. Its no coincidence that many cancer cells carry disabled p53 genes.

Dr. Taipale and his colleagues engineered retinal cells to stop using p53 genes. Just as they had predicted, Crispr now worked much more effectively in these cells.

A team of scientists at the Novartis Institutes for Biomedical Research in Cambridge, Mass., got similar results with a different kind of cells, detailed in a paper also published Monday.

They set out to develop new versions of Crispr to edit the DNA in stem cells. They planned to turn the stem cells into neurons, enabling them to study brain diseases in Petri dishes.

Someday, they hope, it may become possible to use Crispr to create cell lines that can be implanted in the body to treat diseases.

When the Novartis team turned Crispr on stem cells, however, most of them died. The scientists found signs that Crispr had caused p53 to switch on, so they shut down the p53 gene in the stem cells.

Now many of the stem cells survived having their DNA edited.

The authors of both studies say their results raise some concerns about using Crispr to treat human disease.

For one thing, the anticancer defenses in human cells could make Crispr less efficient than researchers may have hoped.

One way to overcome this hurdle might be to put a temporary brake on p53. But then extra mutations may sneak into our DNA, perhaps leading to cancer.

Another concern: Sometimes cells spontaneously acquire a mutation that disables the p53 gene. If scientists use Crispr on a mix of cells, the ones with disabled p53 cells are more likely to be successfully edited.

But without p53, these edited cells would also be more prone to gaining dangerous mutations.

One way to eliminate this risk might be to screen engineered cells for mutant p53 genes. But Steven A. McCarroll, a geneticist at Harvard University, warned that Crispr might select for other risky mutations.

These are important papers, since they remind everyone that genome editing isnt magic, said Jacob E. Corn, scientific director of the Innovative Genomics Institute in Berkeley, Calif.

Crispr doesnt simply rewrite DNA like a word processing program, Dr. Corn said. Instead, it breaks DNA and coaxes cells to put it back together. And some cells may not tolerate such changes.

While Dr. Corn said that rigorous tests for safety were essential, he doubted that the new studies pointed to a cancer risk from Crispr.

The particular kinds of cells that were studied in the two new papers may be unusually sensitive to gene editing. Dr. Corn said he and his colleagues have not found similar problems in their own research on bone marrow cells.

We have all been looking for the possibility of cancer, he said. I dont think that this is a warning for therapies.

We should definitely be cautious, said George Church, a geneticist at Harvard and a founding scientific adviser at Editas.

He suspected that p53s behavior would not translate into any real risk of cancer, but its a valid concern.

And those concerns may be moot in a few years. The problem with Crispr is that it breaks DNA strands. But Dr. Church and other researchers are now investigating ways of editing DNA without breaking it.

Were going to have a whole new generation of molecules that have nothing to do with Crispr, he said. The stock market isnt a reflection of the future.

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A Crispr Conundrum: How Cells Fend Off Gene Editing - The ...

Recommendation and review posted by Jack Burke

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Recommendation and review posted by Rebecca Evans

Cell therapy companies have been rapidly populating over the past few years, making the cell therapy market a high-value, fast-growth market. Key drivers for the market include high rates of cell therapy clinical trials, accelerated pathways for cell therapy product approvals, new technologies to support cell therapy manufacturing, and the potential for cell therapies to revolutionize healthcare.

Additionally, the market gained recent momentum when the Swiss pharmaceutical giant Novartis made history as the first company to win FDA approval for a CAR-T cell therapy in the U.S. in August 2017 (Kymriah).In October 2017, Kite Pharma became the second company to get FDA approval of a CAR-T cell therapy (Yescarta).

These historic events demonstrate to investors, the public and funding providers alike that cell therapy is a market that has emerged, no longer one that is evolving in the future.Today, there are nearly 40 companies developing redirected T cells or NK cells for therapeutic use. There are nearly 70 companies developing stem cell therapeutics (45% of all cell therapy companies). Finally, direct cell reprogramming is gaining popularity as a therapeutic strategy, because of its safety and efficacy advantages.

Because of this rapid market growth, BioInformant has released a global database featuring 150+ cell therapy companies worldwide. It was originally developed in-house for our own purposes, but we have had more and moreclients requesting access to it. For this reason, we updated and expanded it with additional company details. Now, we have officially launched it to the public.

Cell Therapy Companies CAR-T, CAR-NK, Stem Cells, Direct Reprogramming

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Cell Therapy Companies - BioInformant

Recommendation and review posted by simmons

iPS Cells and Therapeutic Applications for Duchenne

We are currently in the optimization/validation phase of pre-clinical development.

This research is being done in the lab of Dr. Rita Perlingeiro at the University of Minnesota, in partnership with the University of Minnesota Center for Translational Medicine and the Molecular and Cellular Therapeutics Facility. This work is currently funded by the Department of Defense (DoD).

Induced pluripotent stem cells (iPS) are adult cells that have been reprogrammed to an embryonic stem cell-like state.There has been tremendous excitement for the therapeutic potential of iPS cells in treating genetic diseases. Our current research builds on our successful proof-of-principle studies for Duchenne performed with mouse wild-type and dystrophic iPS cells as well as control (healthy) human iPS cells. These studies demonstrate equivalent functional myogenic engraftment to that observed with their embryonic counterparts following their transplantation into dystrophic mice.

Our goal now is to apply this technology to clinical grade GMP-compliant iPS cells, and generate a cell product, iPS-derived myogenic progenitors, that can be delivered to muscular dystrophy patients.

Optimization of methodology, characterization of cell product, scalability with GMP-compliant method, followed by safety and efficacy studies. Once these have been achieved, we will be ready to move into a clinical trial.

2-3 years (it depends largely on how much funding we have available to conduct these studies).

University of Minnesota

In the first phase, adults with confirmed diagnosis of Duchenne (> 18 years old).

You can learn more about this research at the website for Dr. Perlingeiros lab: http://www.med.umn.edu/lhi/research/PerlingeiroLab/index.htm

http://www.ClinicalTrials.gov will post all clinical trials once they are actively recruiting patients.

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iPS Cell Therapy - Parent Project Muscular Dystrophy

Recommendation and review posted by Bethany Smith

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Recommendation and review posted by simmons

GeneCopoeia's GeneHero CRISPR-Cas9 products and services provide a complete, powerful solution to your genome editing needs. Products and services include:

CRISPR Plasmids. Transfect cells with our CRISPR plasmids with Cas9 and sgRNA for human, mouse, and rat. Search our database of more than 45,000 human, mouse, and rat genes for genome editing using CRISPR.

CRISPR Lentivirus.Genome integration of CRISPR elements using lentivirus. Cas9 and/or sgRNA packed in purified lentiviral particles at 108 TU/ml, ready to infect all cell types.

CRISPR AAV.Episomal expression of CRISPR components with adeno-associated viralparticles carrying Cas9 and/or sgRNA, excellent for tissue and animal transduction.

Cas9 Stable Cell Lines.Premade Cas9-expressing stable cell lines are great for sgRNA library screening and other high-throughput CRISPR-Cas9 applications.

The clustered, regularly interspaced, short palindromic repeats (CRISPR) system is bacterial immunity mechanism for defense against invading viruses and transposons. This system has been adapted for highly efficient genome editing in many organisms. Compared with earlier genome editing technologies such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), CRISPR-Casmediated gene targeting has similar or greater efficiency. Genome editing has been used for numerous applications, as shown in Table 1.

Table 1. Applications for CRISPR-mediated genome editing.

In the type II CRISPR systems, the complex of a CRISPR RNA (crRNA) annealed to a trans-activating crRNA (tracrRNA) guides the Cas9 endonuclease to a specific genomic sequence, thereby generating double-strand breaks (DSBs) in target DNA. This system has been simplified by fusing crRNA and tracrRNA sequences to produce a synthetic, chimeric single-guided RNA (sgRNA). The sgRNA contains within it a 20 nucleotide DNA recognition sequence (Figure 1).

Figure 1. Mechanism of CRISPR-Cas9-sgRNA target recognition and cleavage.

When the Cas9-sgRNA complex encounters this target sequence in the genome followed by a 3 nucleotide NGG PAM (protospacer adjacent sequence) site, the complex binds to the DNA strand complementary to the target site. Next, the Cas9 nuclease creates a site-specific double-strand break (DSB) 3-4 nucleotides 5' to the PAM. DSBs are repaired by either non-homologous end joining (NHEJ), which is error-prone, and can lead to frameshift mutations, or by homologous recombination (HR) in the presence of a repair template (Figure 2).

Figure 2.CRISPR-Cas9-based gene engineering. Left. DSBs created by sgRNA-guided Cas9-mediated cleavage are repaired by NHEJ. Right. DSBs created by sgRNA-guided Cas9 nuclease are repaired homologous recombination between sequences flanking the DSB site, thereby causing "knock in" of sequences on a donor DNA.

While the CRISPR system provides a highly efficient means for carrying out genome editing applications, it is prone to causing off-target indel mutations. Off-targeting is caused by the ability of the Cas9- sgRNA complex to bind to chromosomal DNA targets with one or more mismatches, or non-Watson-Crick complementary. The propensity of CRISPR for off-target modification is a significant concern for some researchers who want to avoid results that are potentially confounded by off-target modification, as well as for those who might be interested in developing CRISPR for gene therapy applications.

Several strategies have been employed to mitigate CRISPR's propensity for off-target genome modification. One such strategy is to use double nickases to create DSBs. The Cas9 D10A mutant is able to cleave only one DNA strand, thereby creating a "nick". When two sgRNAs that bind on opposite strands flanking the target are introduced, two Cas9 D10A nickase molecules together create a staggered-cut DSB, which is then repaired by either NHEJ or HR (Figure 3). The double nickase strategy has been shown to greatly reduce the frequency of off-target modification. However, double nickases are limited in utility by design constraints; the sgRNAs must be on opposite strands, in opposite orientation to one another, and display optimal activity when spaced from 3-20 nucleotides apart. In addition, the cleavage activity of double nickases tends to be lower than that of standard Cas9-sgRNA. Further, nickases can still cause some degree of off-target indel formation.

Figure 3. General scheme of Cas9 double-nickase strategy. From Ran, et al. (2013). Two additional strategies, the use of truncated (17-18 nucleotide) sgRNAs, as well as a Cas9-FokI fusion, also dramatically reduce CRISPR-mediated off-target genome modification. However, these methods suffer from even further reductions in on-target activity and/or more severe design constraints compared with the double nickase approach.

Recently, two groups demonstrated that engineering Cas9 variants carrying 3-4 amino acid changes virtually eliminates CRISPR off-target genome modification. These variants still retain high on-target activity, without the design constraints of previous approaches, providing a promising alternative for high-fidelity CRISPR-mediated genome editing.

Watch recorded webinar / Download slides Title: Genome Editing: How Do I Use CRISPR? Presented Wednesday, February 22, 2017

Genome Editing-the ability to make specific changes at targeted genomic sites-is fundamentally important to researchers in biology and medicine. CRISPR is a very widely-used method for modifying specific genome sites, and can be used for many applications, including gene knock out, transgene knock in, gene tagging, and correction of genetic defects. However, researchers are often unaware of some of the work required to identify their desired modification in their cell lines. In this webinar, we discuss what you need to do for CRISPR genome editing after you have obtained your reagents from GeneCopoeia, the so-called Downstream work.

Watch recorded webinar / Download slides Title: GeneCopoeia CRISPR Genome Editing Technology Presented Wednesday, January 25, 2017

The ability to make specific changes at targeted genomic sites in complex organisms is fundamentally important to researchers in biology and medicine. Researchers have developed and refined chimeric DNA endonucleases, such as CRISPR-Cas9, to stimulate double strand breaks at defined genomic loci, allowing the ability to insert, delete, and replace genetic information at will. These tools can also be used without nucleases to induce or repress gene transcription. In this webinar, we discuss CRISPR and other genome editing technologies and the applications they make possible, and provide information on GeneCopoeia's powerful suite of genome editing products and services.

Watch recorded webinar / Download slides Title: Applications For CRISPR-Cas9 Stable Cell Lines Presented Wednesday, March 22, 2017

The CRISPR-Cas9 system has become greatly popular for genome editing in recent years, due to its ease-of-design, efficiency, specificity, and relatively low cost. In mammalian cell culture systems, most genome editing is achieved using transient transfection or lentiviral transduction, which works well for routine, low-throughput applications. However, for other applications, it would be beneficial to have a system in which one component, namely the CRISPR-Cas9 nuclease, was stably integrated into the genome. In this webinar, we introduce GeneCopoeias suite of Cas9 stable cell lines, and discuss the great utility that these cell lines provide for genome editing applications.

Watch recorded webinar / Download slides Title: Safe Harbor Transgenesis in Human & Mouse Genome Editing Presented Wednesday, April 19, 2017

Insertion of transgenes in mammalian chromosomes is an important approach for biomedical research and targeted gene therapy. Traditional lentiviral-mediated transgenesis is effective and straightforward, but its random integration can often be unstable and harm cells. "Safe Harbor" sites in human and mouse chromosomes have been employed recently as an alternative to random, viral-mediated integration because they support consistent, stable expression, and are not known to hamper cell fitness or growth. In this webinar, we will discuss the merits of Safe harbor transgenesis approaches, and how GeneCopoeia's CRISPR tools for Safe Harbor knock-in can greatly benefit your research.

Watch recorded webinar / Download slides Title: GeneCopoeia CRISPR sgRNA Libraries For Functional Genomics Presented Wednesday, April 29, 2015

Biomedical researchers are enjoying a Renaissance in functional genomics, which aims to use a wealth of DNA sequence informationmost notably, the complete sequence of the human genometo determine the natural roles of the genes encoded by the genome. As a result, biochemical networks and pathways will be better understood, with the hope of leading to improved disease treatments. Researchers are turning increasingly to CRISPR (clustered, regularly interspaced, short palindromic repeats) for functional genomics studies. Several groups recently adapted CRISPR for high-throughput knockout applications, by developing large-scale CRISPR sgRNA libraries. GeneCopoeia recently launched a number of smaller, pathway- and gene group-focused CRISPR sgRNA libraries, which offer several key advantages over the whole-genome libraries. In this 40 minute webinar, we discuss the merits and applications for CRISPR sgRNA libraries, how to use CRISPR sgRNA libraries, the advantages of using small, pathway- and gene group-focused libraries, and how GeneCopoeia can help you with your high-throughput CRISPR knockout studies.

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Answer:If you are doing simple gene knockouts in humans or mice, you can order CRISPR sgRNAs on our website. All you need to do is go to the , search for your gene, and then choose the appropriate clones that will work for your system. These CRISPR sgRNAs are designed by default to knock out all possible known and predicted transcript variants of your gene, and are targeted early in the coding regions. You can also order donor clones for these knockouts from the search results page. If you are doing a different application, such as introducing a point mutation, then you will need to and, after determining what you need, we will send you a custom quote.

Answer:For sgRNA clones (including both all-in-one Cas9/sgRNA clones and sgRNA-only clones, the default delivery format is bacterial stock. You have the option of ordering purified DNA for these clones for an additional charge. For HDR donor clones, the default delivery format is purified DNA.

Answer:The turnaround time for sgRNA clones (including both all-in-one Cas9/sgRNA clones and sgRNA-only clones) is 2-3 weeks. The turnaround time for HDR donor clones depends greatly on the nature of the modification that the clone is being used for. For HDR donor clones used for simple knockout, the turnaround time is 2-4 weeks. Other HDR donor clones, such as those used for fusion tagging or mutagenesis, can take 6-8 weeks, but can also take longer.

Answer:Yes. We sequence the inserts of each CRISPR sgRNA clone, and provide you with datasheets that show the full sequence of each clone (including HDR donor clones), a map, restriction enzyme digestions sites, and suggested sequencing primers. To obtain these datasheets, you just need to visit our on our website. You will need an account on our website, your catalog number(s), and your sales order number.

Answer:In the presence of drug, the only way for cells to survive is to integrate the plasmid into the chromosome, so it is possible to get drug-resistant clones that were only transfected with the donor plasmid. However, such integration is random. CRISPR increases donor targeting frequency by several orders of magnitude.

Answer:Our genome editing products can be used for virtually all species. Our standard plasmids for CRISPR are designed for work in mammalian cells. In addition, these plasmids can be used as templates for T7 promoter-driven in vitro transcription, for introduction into mice, zebrafish, Drosophila, and many other model organisms. Further, we can generate custom constructs that can be used in a wide variety of organisms.

Answer:Yes. The donor must be present when the DSB is formed in order to be used as a repair template. Otherwise, the cell must use non-homologous end joining (NHEJ) in order to repair the DSB, because unrepaired DSBs are lethal.

Answer:Our CRISPR plasmids typically do not integrate into the host genome in transfection experiments. However, after clonal selection for edited cells, we recommend screening clones for those which have lost the nuclease plasmids. This can be done by testing clones to see if they have become sensitive to the antibiotic of the resistance gene on the plasmid, or if they no longer express the plasmid's fluorescent marker (where applicable). Our lentiviral clones are expected to integrate randomly into chromosomes.

1. If you are making an insertion or deletion, the easiest way to screen your cells is by PCR using primers flanking the modified site, provided that the insertion or deletion is large enough to detect by standard agarose gel electrophoresis.

2. For very small insertions or deletions, you can screen your clones using GeneCopoeia's IndelCheck T7 endonuclease I assay, which is a method that detects mutations by cleaving double stranded DNA containing a mismatch. You can also screen using Sanger sequencing of PCR products.

3. If you are introducing a point mutation, then you can use either real-time PCR or Sanger sequencing to detect the modification.

4. If the modification you are introducing creates or destroys a restriction enzyme site, then enzyme cleavage of PCR products can be used to distinguish between modified and unmodified alleles.

5. Finally, either Sanger sequencing of PCR products or Next Generation sequencing of whole genomes can be used to screen for modifications. Regardless of which screening method you choose, it is also important that you are able to determine whether only a portion or all of the alleles have been modified.

In order to reduce the amount of time and effort required to identify edited clones, GeneCopoeia recommends our donor plasmid design and construction service. We will construct a donor plasmid that contains a defined modification, flanked by a selectable marker such as puromycin resistance, and homologous arms from your target region. The donor may or may not also include a fluorescent reporter such as GFP. The markers can be flanked by loxP sites, to permit Cre-mediated removal, if desired. Use of a GeneCopoeia-designed donor plasmid allows you to select for edited clones and reduces the number of clones required for screening. You can also purchase our donor cloning vectors for do-it-yourself donor clone construction.

Answer:Yes. Even though frameshifts are not possible with miRNAs and other noncoding RNAs, an indel occurring in a critical region, such as the mature sequence of a miRNA, should be enough to abolish its function.

Answer:The vector backbones of our CRISPR sgRNAs are designed to not replicate in the host. These plasmids, which are transiently transfected, will typically be lost after several rounds of cell division and will not further affect the host cell. After transfection, cells are plated at low density to promote the formation of single colonies. These colonies should be screened to ensure that they have lost the plasmid(s). This can be done by testing clones to see if they have become sensitive to the antibiotic of the resistance gene on the plasmid, or if they no longer express the plasmid's fluorescent marker (where applicable). However, even if the TALEN or CRISPR plasmid integrates, it can no longer cut the site after it is edited, because NHEJ destroys the TALEN or sgRNA recognition site. To be completely assured that the transfection is transient, we recommend delivering RNA instead of plasmid DNA. If you are using HDR, we recommend engineering synonymous mutations into the donor to destroy the TALEN or sgRNA recognition site.

Answer:Yes. CRISPR has been shown to be able to disrupt multiple copies at once. The efficiency varies depending on different factors, such as cell type, transfection efficiency and TALEN/CRISPR activity.

Answer:Yes. We have the reagents for the Cas9 D10A nickase, and have successfully tested our double nickase designs. However, in order to create mutagenic DSBs, the nickase requires the correct targeting of two appropriately-spaced sgRNAs on opposite strands, flanking the break site. Because proper sgRNA targeting requires the presence of the N-G-G PAM site immediately following the recognition site, it might not always be possible to use the nickase for DSB formation. There are also high-fidelity variants of Cas9 nuclease that edit genes with greater specificity than wild type Cas9, but sometimes with reduced efficacy and with increased design constraints. However, since these high fidelity variants use only one sgRNA, they are easier to work with than Cas9 niclases.

Answer:Yes. To create a DSB, the nickase requires the correct targeting of two appropriately-spaced sgRNAs on opposite strands, flanking the break site. This is sufficient to stimulate HDR between the target site and the donor. While this method has the advantage of potentially fewer off-target NHEJ-mediated mutations, since single strand nicks are repaired with higher fidelity than DSBs, it is not without limitations. Proper sgRNA targeting requires the presence of the N-G-G PAM site immediately following the recognition site. Therefore, it might not always be possible to use the nickase for HDR.

Answer:We only sell plasmids containing our custom-designed CRISPR sgRNAs. If you need a negative control, we also sell a CRISPR plasmid containing a scrambled sgRNA.

Answer:Yes.

Answer:Yes. There is a double mutant of the Cas9 nuclease that completely abolishes nuclease activity. This mutant can be fused to a transcriptional modulator such as VP64 and targeted to specific genes. You can also use the catalytically dead Cas9 with properly-designed sgRNAs to repress, or interfere with, gene expression.

Answer:Yes. We have both non-viral and lentiviral formats. We also have , in which we can provide you with lentiviral particles expressing both Cas9 and sgRNAs.

Answer:Unfortunately, no. Lentiviruses enter cells as RNA, but HDR donors must enter the cells as DNA at the same time as Cas9 and the sgRNAs.

Answer:Lentiviral particles, transfection-ready DNA, and bacterial stock.

Answer:Yes. The lentiviral plasmids are "dual-use", so that they can either be packaged into lentiviral particles or transfected into cells by standard transfection methods.

Answer:Our sgRNA representation does not need to be validated by Next Generation Sequencing. Each library is small compared with the genome-wide libraries, and each sgRNA clone is constructed individually, cultured in E. coli individually, then pooled as E. coli in approximately equal amounts. From those pools we prepare DNA and then, if necessary, lentiviral particles.

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GeneHero CRISPR Products and Services | Genecopoeia

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