Archive for the ‘Gene Therapy Doctor’ Category

February 18, 2016 5:55 PM By Dr. Maria Simbra

PITTSBURGH (KDKA) When part of the brain is no longer working properly, would it be possible to put something in to boost function?

Neurosurgeon Dr. Mark Richardson is trying to find out.

What were trying to do with this study is to replace an enzyme thats lost as cells degenerate in Parkinsons disease, Dr. Richardson said. The enzyme helps the brain make dopamine.

The brain chemical dopamine is important to keeping movements smooth. The problem in Parkinsons disease is the lack of dopamine because of worn out brain cells, and you end up with shaking, stiffness, and slowness of movement.

People can take medicine for Parkinsons disease, but there can be symptom fluctuations and at higher doses, side effects.

Typically in Parkinsons disease, these symptoms kind of go up and down like this, and they can be masked very well by medication, but unfortunately what tends to happen for all of these patients is progression to more of a roller coaster ride of ups and downs during the day, Dr. Richardson said.

Dr. Richardson is leading part of a study, first funded by the Michael J. Fox Foundation and now by a biotherapy company, to see whether inserting a gene into a specific part of the brain will be the on switch for more dopamine production.

The idea of brain surgery for a chronic disease is very different than continuing to take medication, Dr. Richardson said.

The gene is delivered into the brain through the skull by a thin tube and carried by a virus

The idea of a virus probably sounds very scary to some people. But, this virus cannot reproduce, Dr. Richardson said. It can insert itself into a cell, and it can only do one thing there. It can release the gene to allow this enzyme to be made.

Dr. Richardson and the lead investigator in San Francisco are looking for 20 patients to participate. They will be followed for three years, and their need for medication will be evaluated and compared before and after.

To qualify you have to be between 40 and 70 and on certain medicines for Parkinsons disease for at least three years with increasing fluctuations in movement.

Dr. Richardson hopes gene therapy leads to smoother days and fewer symptoms.

If we can show this is a small group of patients, the trial will be expanded, Dr. Richardson said. With a little bit of luck, within the next decade, we will see a gene therapy accepted as a proven and viable treatment option.

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Dr. Maria Simbra is a multi award-winning medical journalist, who brings a unique set of skills to her position as medical reporter on KDKA-TV. A member of the KDKA news team since May 2002, this physician and formally trained journalism professi...

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GENE THERAPY:

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Caveat:

Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. I have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publishing this article. However, in view of the possibility of human error or changes in medical sciences, I do not assure that the information contained herein is in every respect accurate or complete, and I disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. I have taken some information from articles that were published few years ago. The facts and conclusions presented may have since changed and may no longer be accurate. Questions about personal health should always be referred to a physician or other health care professional.

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Prologue:

BLASPHEMY! some cried when the concept of gene therapy first surfaced. For them tinkering with the genetic constitution of human beings was equivalent to playing God, and this they perceived as being sacrilegious! On the other side was the scientific community, abuzz with excitement at the prospect of being able to wipe certain genetic disorders in humans entirely from the human gene pool. Although the term gene therapy was first introduced during the 1980s, the controversy about the rationality of this line of treatment still rages on. In the center of the debate lie the gene therapy pros and cons that derive opinions from religious, ethical and undoubtedly, political domains. The concept of genes as carriers of phenotypic information was introduced in the early 19th century by Gregor Mendel, who later demonstrated the properties of genetic inheritance in peas. Over the next 100 years, many significant discoveries lead to the conclusions that genes encode proteins and reside on chromosomes, which are composed of DNA. These findings culminated in the central dogma of molecular biology, that proteins are translated from RNA, which is transcribed from DNA. James Watson was quoted as saying we used to think that our fate was in our stars, but now we know, in large measures, our fate is in our genes. Genes, the functional unit of heredity, are specific sequences bases that encode instructions to make proteins. Although genes get a lot of attentions, it is the proteins that perform most life functions. When genes are altered, encoded proteins are unable to carry out their normal functions, resulting in genetic disorders. Gene therapy is a novel therapeutic branch of modern medicine. Its emergence is a direct consequence of the revolution heralded by the introduction of recombinant DNA methodology in the 1970s. Gene therapy is still highly experimental, but has the potential to become an important treatment regimen. In principle, it allows the transfer of genetic information into patient tissues and organs. Consequently, diseased genes can be eliminated or their normal functions rescued. Furthermore, the procedure allows the addition of new functions to cells, such as the production of immune system mediator proteins that help to combat cancer and other diseases. Most scientists believe the potential for gene therapy is the most exciting application of DNA science, yet undertaken.

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Note:

Please read my other articles Stem cell therapy and human cloning, Cell death and Genetically modified before reading this article.

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The rapid pace of technological advances has profound implications for medical applications far beyond their traditional roles to prevent, treat, and cure disease. Cloning, genetic engineering, gene therapy, human-computer interfaces, nanotechnology, and designer drugs have the potential to modify inherited predispositions to disease, select desired characteristics in embryos, augment normal human performance, replace failing tissues, and substantially prolong life span. As gene therapy is uprising in the field of medicine, scientists believe that after 20 years, this will be the last cure of every genetic disease. Genes may ultimately be used as medicine and given as simple intravenous injection of gene transfer vehicle that will seek our target cells for stable, site-specific chromosomal integration and subsequent gene expression. And now that a draft of the human genome map is complete, research is focusing on the function of each gene and the role of the faulty gene play in disease. Gene therapy will ultimately play Copernican part and will change our lives forever.

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Gene therapy, the experimental therapy as on today:

Gene therapy is an experimental technique that uses genes to treat or prevent diseases. Genes are specific sequences of bases that encode instructions on how to make proteins. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is used for correcting defective genes responsible for disease development. Researchers may use one of several approaches for correcting faulty genes. Although gene therapy is a promising treatment which helps successfully treat and prevent various diseases including inherited disorders, some types of cancer, and certain viral infections, it is still at experimental stage. Gene therapy is presently only being tested for the treatment of diseases that have no other cures. Currently, the only way for you to receive gene therapy is to participate in a clinical trial. Clinical trials are research studies that help doctors determine whether a gene therapy approach is safe for people. They also help doctors understand the effects of gene therapy on the body. Your specific procedure will depend on the disease you have and the type of gene therapy being used.

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Introduction to gene therapy:

Gene therapy is a clinical strategy involving gene transfer with therapeutic purposes. It is based on the concept that an exogenous gene (transgene) is able to modify the biology and phenotype of target cells, tissues and organs. Initially designed to definitely correct monogenic disorders, such as cystic fibrosis, severe combined immunodeficiency or muscular dystrophy, gene therapy has evolved into a promising therapeutic modality for a diverse array of diseases. Targets are expanding and currently include not only genetic, but also many acquired diseases, such as cancer, tissue degeneration or infectious diseases. Depending on the duration planned for the treatment, type and location of target cells, and whether they undergo division or are quiescent, different vectors may be used, involving nonviral methods, non-integrating viral vectors or integrating viral vectors. The first gene therapy clinical trial was carried out in 1989, in patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral transduction. In the early nineties, a clinical trial with children with severe combined immunodeficiency (SCID) was also performed, by retrovirus transfer of adenosine deaminase gene to lymphocytes isolated from these patients. Since then, more than 5,000 patients have been treated in more than 1,000 clinical protocols all over the world. Despite the initial enthusiasm, however, the efficacy of gene therapy in clinical trials has not been as high as expected; a situation further complicated by ethical and safety concerns. Further studies are being developed to solve these limitations.

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Historical development of gene therapy:

Chronology of development of gene therapy technology:

1970s, 1980s and earlier:

In 1972 Friedmann and Roblin authored a paper in Science titled Gene therapy for human genetic disease? Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects. However, these authors concluded that it was premature to begin gene therapy studies in humans because of lack of basic knowledge of genetic regulation and of genetic diseases, and for ethical reasons. They did, however, propose that studies in cell cultures and in animal models aimed at development of gene therapies be undertaken. Such studiesas well as abortive gene therapy studies in humanshad already begun as of 1972. In the 1970s and 1980s, researchers applied such technologies as recombinant DNA and development of viral vectors for transfer of genes to cells and animals to the study and development of gene therapies.

1990s:

The first approved gene therapy case in the United States took place on 14 September 1990, at the National Institute of Health, under the direction of Professor William French Anderson. It was performed on a four year old girl named Ashanti DeSilva. It was a treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The effects were only temporary, but successful. New gene therapy approach repairs errors in messenger RNA derived from defective genes. This technique has the potential to treat the blood disorder thalassaemia, cystic fibrosis, and some cancers. Researchers at Case Western Reserve University and Copernicus Therapeutics are able to create tiny liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane. Sickle-cell disease is successfully treated in mice. The mice which have essentially the same defect that causes sickle cell disease in humans through the use a viral vector, were made to express the production of fetal hemoglobin (HbF), which normally ceases to be produced by an individual shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF has long been shown to temporarily alleviate the symptoms of sickle cell disease. The researchers demonstrated this method of gene therapy to be a more permanent means to increase the production of the therapeutic HbF. In 1992 Doctor Claudio Bordignon working at the Vita-Salute San Raffaele University, Milan, Italy performed the first procedure of gene therapy using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases. In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase-deficiency (SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or bubble boy disease) held from 2000 and 2002 was questioned when two of the ten children treated at the trials Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the United States, the United Kingdom, France, Italy, and Germany. In 1993 Andrew Gobea was born with severe combined immunodeficiency (SCID). Genetic screening before birth showed that he had SCID. Blood was removed from Andrews placenta and umbilical cord immediately after birth, containing stem cells. The allele that codes for ADA was obtained and was inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses entered and inserted the gene into the stem cells chromosomes. Stem cells containing the working ADA gene were injected into Andrews blood system via a vein. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed. The 1999 death of Jesse Gelsinger in a gene therapy clinical trial resulted in a significant setback to gene therapy research in the United States. Jesse Gelsinger had ornithine transcarbamylase deficiency. In a clinical trial at the University of Pennsylvania, he was injected with an adenoviral vector carrying a corrected gene to test the safety of use of this procedure. He suffered a massive immune response triggered by the use of the viral vector, and died four days later. As a result, the U.S. FDA suspended several clinical trials pending the re-evaluation of ethical and procedural practices in the field.

2003:

In 2003 a University of California, Los Angeles research team inserted genes into the brain using liposomes coated in a polymer called polyethylene glycol. The transfer of genes into the brain is a significant achievement because viral vectors are too big to get across the bloodbrain barrier. This method has potential for treating Parkinsons disease. RNA interference or gene silencing may be a new way to treat Huntingtons disease. Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.

2006:

In March 2006 an international group of scientists announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and which gives a defective immune system. The study, published in Nature Medicine, is believed to be the first to show that gene therapy can cure diseases of the myeloid system. In May 2006 a team of scientists led by Dr. Luigi Naldini and Dr. Brian Brown from the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) in Milan, Italy reported a breakthrough for gene therapy in which they developed a way to prevent the immune system from rejecting a newly delivered gene. Similar to organ transplantation, gene therapy has been plagued by the problem of immune rejection. So far, delivery of the normal gene has been difficult because the immune system recognizes the new gene as foreign and rejects the cells carrying it. To overcome this problem, the HSR-TIGET group utilized a newly uncovered network of genes regulated by molecules known as microRNAs. Dr. Naldinis group reasoned that they could use this natural function of microRNA to selectively turn off the identity of their therapeutic gene in cells of the immune system and prevent the gene from being found and destroyed. The researchers injected mice with the gene containing an immune-cell microRNA target sequence, and the mice did not reject the gene, as previously occurred when vectors without the microRNA target sequence were used. This work will have important implications for the treatment of hemophilia and other genetic diseases by gene therapy. In August 2006, scientists at the National Institutes of Health (Bethesda, Maryland) successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells. This study constitutes one of the first demonstrations that gene therapy can be effective in treating cancer. In November 2006 Preston Nix from the University of Pennsylvania School of Medicine reported on VRX496, a gene-based immunotherapy for the treatment of human immunodeficiency virus (HIV) that uses a lentiviral vector for delivery of an antisense gene against the HIV envelope. In the Phase I trial enrolling five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens, a single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was safe and well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. In addition, all five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in U.S. Food and Drug Administration-approved human clinical trials for any disease. Data from an ongoing Phase I/II clinical trial were presented at CROI 2009.

2007:

On 1 May 2007 Moorfields Eye Hospital and University College Londons Institute of Ophthalmology announced the worlds first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23 year-old British male, Robert Johnson, in early 2007. Lebers congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in New England Journal of Medicine in April 2008. They researched the safety of the subretinal delivery of recombinant adeno-associated virus (AAV) carrying RPE65 gene, and found it yielded positive results, with patients having modest increase in vision, and, perhaps more importantly, no apparent side-effects.

2008:

In May 2008, two more groups, one at the University of Florida and another at the University of Pennsylvania, reported positive results in independent clinical trials using gene therapy to treat Lebers congenital amaurosis. In all three clinical trials, patients recovered functional vision without apparent side-effects. These studies, which used adeno-associated virus, have spawned a number of new studies investigating gene therapy for human retinal disease.

2009:

In September 2009, the journal Nature reported that researchers at the University of Washington and University of Florida were able to give trichromatic vision to squirrel monkeys using gene therapy, a hopeful precursor to a treatment for color blindness in humans. In November 2009, the journal Science reported that researchers succeeded at halting a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.

2010:

A paper by Komromy et al. published in April 2010, deals with gene therapy for a form of achromatopsia in dogs. Achromatopsia, or complete color blindness, is presented as an ideal model to develop gene therapy directed to cone photoreceptors. Cone function and day vision have been restored for at least 33 months in two young dogs with achromatopsia. However, the therapy was less efficient for older dogs. In September 2010, it was announced that an 18 year old male patient in France with beta-thalassemia major had been successfully treated with gene therapy. Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions. A team directed by Dr. Phillipe Leboulch (of the University of Paris, Bluebird Bio and Harvard Medical School) used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007. The patients haemoglobin levels were stable at 9 to 10 g/dL, about a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions had not been needed. Further clinical trials were planned. Bone marrow transplants are the only cure for thalassemia but 75% of patients are unable to find a matching bone marrow donor.

2011:

In 2007 and 2008, a man being treated by Gero Htter was cured of HIV by repeated Hematopoietic stem cell transplantation with double-delta-32 mutation which disables the CCR5 receptor; this cure was not completely accepted by the medical community until 2011. This cure required complete ablation of existing bone marrow which is very debilitating. In August 2011, two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The study carried out by the researchers at the University of Pennsylvania used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease. In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free. Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.

2012:

The FDA approves clinical trials of the use of gene therapy on thalassemia major patients in the US. Researchers at Memorial Sloan Kettering Cancer Center in New York begin to recruit 10 participants for the study in July 2012. The study is expected to end in 2014. In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment, called Alipogene tiparvovec (Glybera), compensates for lipoprotein lipase deficiency (LPLD), which can cause severe pancreatitis. People with LPLD cannot break down fat, and must manage their disease with a restricted diet. However, dietary management is difficult, and a high proportion of patients suffer life-threatening pancreatitis. The recommendation was endorsed by the European Commission in November 2012 and commercial rollout is expected in late 2013. In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission or very close to it three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1 which exist only on cancerous myeloma cells.

2013:

In March 2013, Researchers at the Memorial Sloan-Kettering Cancer Center in New York, reported that three of five subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients immune systems would make normal T-cells and B-cells after a couple of months however they were given bone marrow to make sure. One patient had relapsed and died and one had died of a blood clot unrelated to the disease. Following encouraging Phase 1 trials, in April 2013, researchers in the UK and the US announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients at several hospitals in the US and Europe to use gene therapy to combat heart disease. These trials were designed to increase the levels of SERCA2a protein in the heart muscles and improve the function of these muscles. The FDA granted this a Breakthrough Therapy Designation which would speed up the trial and approval process in the USA. In July 2013 the Italian San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) reported that six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months the results were promising. Three of the children had metachromatic leukodystrophy which causes children to lose cognitive and motor skills. The other children had Wiskott-Aldrich syndrome which leaves them to open to infection, autoimmune diseases and cancer due to a faulty immune system. In October 2013, the Great Ormond Street Hospital, London reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and their immune systems were showing signs of full recovery. Another three children treated since then were also making good progress. ADA-SCID children have no functioning immune system and are sometimes known as bubble children. In October 2013, Amit Nathswani of the Royal Free London NHS Foundation Trust in London reported that they had treated six people with haemophilia in early 2011 using genetically engineered adeno-associated virus. Over two years later all six were still producing blood plasma clotting factor.

2014:

In January 2014, researchers at the University of Oxford reported that six people suffering from choroideremia had been treated with a genetically engineered adeno-associated virus with a copy of a gene REP1. Over a six month to two year period all had improved their sight. Choroideremia is an inherited genetic eye disease for which in the past there has been no treatment and patients eventually go blind. In March 2014 researchers at the University of Pennsylvania reported that 12 patients with HIV had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation known to protect against HIV (CCR5 deficiency). Results were promising.

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The three main issues for the coming decade will be public perceptions, scale-up and manufacturing, and commercial considerations. Focusing on single-gene applications, which tend to be rarer diseases, will produce successful results sooner than the current focus on the commoner, yet more complex, cancer and heart diseases.

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What is Gene?

A gene is an important unit of hereditary information. It provides the code for living organisms traits, characteristics, function, and physical development. Each person has around 25,000 genes that are located on 46 chromosomes. Gene is a segment of DNA found on chromosome that codes for a particular protein. It acts as a blue print for making enzymes and other proteins for every biochemical reaction and structure of body.

What is allele?

Alleles are two or more alternative forms of a gene that can occupy a specific locus (location) on a chromosome.

What is DNA?

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic information used in the development and function of all known living organisms. The main role of DNA is the long-term storage of information. DNA is often compared to a set of blueprints or a recipe or code, since it contains the instructions needed to construct other components of cells, such as proteins. The DNA segments that carry this genetic information are called genes.

What are Chromosomes?

A chromosome is a singular piece of DNA, which contains many genes. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. Chromosomes are found inside the nucleus of cells.

What are Proteins?

Proteins are large organic compounds made of amino acids. They are involved in many processes within cells. Proteins act as building blocks, or function as enzymes and are important in communication among cells.

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What are plasmids?

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Plasmid is any extrachromosomal heritable determinant. Plasmids are fragments of double-stranded DNA that can replicate independently of chromosomal DNA, and usually carry genes. Although they can be found in Bacteria, Archaea and Eukaryotes, they play the most significant biological role in bacteria where they can be passed from one bacterium to another by horizontal gene transfer, usually providing a context-dependent selective advantage, such as antibiotic resistance.

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In the center of every cell in your body is a region called the nucleus. The nucleus contains your DNA which is the genetic code you inherited from each of your parents. The DNA is ribbon-like in structure, but normally exists in a condensed form called chromosomes. You have 46 chromosomes (23 from each parent), which are in turn comprised of thousands of genes. These genes encode instructions on how to make proteins. Proteins make up the majority of a cells structure and perform most life functions. Genes tell cells how to work, control our growth and development, and determine what we look like and how our bodies work. They also play a role in the repair of damaged cells and tissues. Each person has more than 25,000 genes, which are made up of DNA. You have 2 copies of every gene, 1 inherited from your mother and 1 from your father.

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DNA or deoxyribonucleic acid is the very long molecule that encodes the genetic information. A gene is a stretch of DNA required to make a functional product such as part or all of a protein. People have about 25,000 genes. During gene therapy, DNA that codes for specific genes is delivered to individual cells in the body.

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The Human Genome:

The human genome is the entire genetic code that resides in every cell in your body (with the exception of red blood cells). The genome is divided into 23 chromosome pairs. During reproduction, two copies of the chromosomes (one from each parent) are passed onto the offspring. While most chromosomes are identical for males and females, the exceptions are the sex chromosomes (known as the X and Y chromosomes). Each chromosome contains thousands of individual genes. These genes can be further divided into sequences called exons and introns, which are in turn made up of even shorter sequences called codons. And finally, the codons are made up of base pairs, combinations of four bases: adenine, cytosine, thymine, and guanine. Or A, C, T, and G for short. The human genome is vast, containing an estimated 3.2 billion base pairs. To put that in perspective, if the genome was a book, it would be hundreds of thousands of pages long. Thats enough room for a dozen copies of the entire Encyclopaedia Britannica, and all of it fits inside a microscopic cell.

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Our genes help make us unique. Inherited from our parents, they go far in determining our physical traits like eye color and the color and texture of our hair. They also determine things like whether babies will be male or female, the amount of oxygen blood can carry, and the likelihood of getting certain diseases. Scientists believe that every human has about 25,000 genes per cell. A mutation, or change, in any one of these genes can result in a disease, physical disability, or shortened life span. These mutations can be passed from one generation to another, inherited just like a mothers curly hair or a fathers brown eyes. Mutations also can occur spontaneously in some cases, without having been passed on by a parent. With gene therapy, the treatment or elimination of inherited diseases or physical conditions due to these mutations could become a reality. Gene therapy involves the manipulation of genes to fight or prevent diseases. Put simply, it introduces a good gene into a person who has a disease caused by a bad gene. Variations on genes are known as alleles. Because of changes in the genetic code caused by mutations, there are often more than one type of gene in the gene pool. For example, there is a specific gene to determine a persons blood type. Therefore, a person with blood type A will have a different version of that gene than a person with blood type B. Some genes work in tandem with each other.

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Genes to protein:

Chromosomes contain long chains of DNA built with repeating subunits known as nucleotides. That means a single gene is a finite stretch of DNA with a specific sequence of nucleotides. Those nucleotides act as a blueprint for a specific protein, which gets assembled in a cell using a multistep process.

1. The first step, known as transcription, begins when a DNA molecule unzips and serves as a template to create a single strand of complementary messenger RNA.

2. The messenger RNA then travels out of the nucleus and into the cytoplasm, where it attaches to a structure called the ribosome.

3. There, the genetic code stored in the messenger RNA, which itself reflects the code in the DNA, determines a precise sequence of amino acids. This step is known as translation, and it results in a long chain of amino acids a protein.

Proteins are the workhorses of cells. They help build the physical infrastructure, but they also control and regulate important metabolic pathways. If a gene malfunctions if, say, its sequence of nucleotides gets scrambled then its corresponding protein wont be made or wont be made correctly. Biologists call this a mutation, and mutations can lead to all sorts of problems, such as cancer and phenylketonuria. Gene therapy tries to restore or replace a defective gene, bringing back a cells ability to make a missing protein.

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Length measurements of DNA/RNA:

The following abbreviations are commonly used to describe the length of a DNA/RNA molecule:

bp = base pair(s) one bp corresponds to approximately 3.4 (340 pm) of length along the strand, or to roughly 618 or 643 daltons for DNA and RNA respectively.

kb (= kbp) = kilo base pairs = 1,000 bp

Mb = mega base pairs = 1,000,000 bp

Gb = giga base pairs = 1,000,000,000 bp.

For case of single-stranded DNA/RNA units of nucleotides are used, abbreviated nt (or knt, Mnt, Gnt), as they are not paired.

Note:

Please do not confuse these terms with computer data units.

kb in molecular biology is kilobase pairs = 1000 base pairs

kb in computer data is kilobytes = 1000 bytes

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Read this article:
Dr Rajiv Desai Blog Archive GENE THERAPY

In the 1990s there was great hope that this novel approach may provide an answer to many hitherto incurable diseases. The basic idea is to correct defective genes responsible for disease development. This can be achieved in a number of ways:

When a normal gene is inserted into the genome, a carrier molecule (a vector) is used. This will deliver the new gene to the target cells. The most commonly used vectors are viruses. The most commonly used viruses are:

These viruses are altered to carry normal human DNA. The patient's target cells are infected with the vector, which deposits its genetic load including the gene to be replaced . The target cell is then able to produce a functioning protein. More recently, success has been seen by combining a tumour-specific adenovirus vector and several single therapy genes. Targeting gene-virotherapy has killed tumour cells with minimal damage to normal cells in mice.[1][2] There are also nonviral insertion options. The simplest method is direct introduction of new DNA into the target tissues. This is limited by the type of tissue and the amount of DNA required. An artificial lipid sphere with an aqueous core is created - a liposome - which can both carry the therapeutic DNA and pass it through the target cells membrane. The therapeutic DNA can also bind chemically to molecules that will attach to target cell receptor sites. These are then taken into the cell's interior. This tends to be less effective than the other methods.

Human gene therapy is still largely in the experimental phase. There have been few big breakthroughs since the first trial started in 1990. There has also been at least one death attributed to therapy and two cases of leukaemia developing post-therapy. There are also technical problems involved:

In a bid to alleviate disease at the earliest possible stage, in utero fetal gene therapy has also been tried.[6] Prenatal screening for severe genetic disease such as Crigler-Najjar syndrome, Pompe's disease and haemophilia B has been tested in mouse models. There have been issues with the development of liver tumours, insufficient target cells are reached and the therapy is not toxic enough to target cells. There are attempts underway to manufacture antitumour vaccines.In this technique Epstein-Barr virus vectors mediate gene transfer into human B lymphocytes.[7] Other areas of research include:

A recent trial, approved by the American Food and Drug Administration, is for the treatment of Parkinson's disease. This is a phase 1 clinical trial with 11 patients already enrolled. They are aiming to produce the neuroprotective and restorative subthalamic glutamic decarboxylase. There have been no adverse events reported to date.[13]

Read more here:
Gene Therapy | Doctor | Patient

In the 1990s there was great hope that this novel approach may provide an answer to many hitherto incurable diseases. The basic idea is to correct defective genes responsible for disease development. This can be achieved in a number of ways:

When a normal gene is inserted into the genome, a carrier molecule (a vector) is used. This will deliver the new gene to the target cells. The most commonly used vectors are viruses. The most commonly used viruses are:

These viruses are altered to carry normal human DNA. The patient's target cells are infected with the vector, which deposits its genetic load including the gene to be replaced . The target cell is then able to produce a functioning protein. More recently, success has been seen by combining a tumour-specific adenovirus vector and several single therapy genes. Targeting gene-virotherapy has killed tumour cells with minimal damage to normal cells in mice.[1][2] There are also nonviral insertion options. The simplest method is direct introduction of new DNA into the target tissues. This is limited by the type of tissue and the amount of DNA required. An artificial lipid sphere with an aqueous core is created - a liposome - which can both carry the therapeutic DNA and pass it through the target cells membrane. The therapeutic DNA can also bind chemically to molecules that will attach to target cell receptor sites. These are then taken into the cell's interior. This tends to be less effective than the other methods.

Human gene therapy is still largely in the experimental phase. There have been few big breakthroughs since the first trial started in 1990. There has also been at least one death attributed to therapy and two cases of leukaemia developing post-therapy. There are also technical problems involved:

In a bid to alleviate disease at the earliest possible stage, in utero fetal gene therapy has also been tried.[6] Prenatal screening for severe genetic disease such as Crigler-Najjar syndrome, Pompe's disease and haemophilia B has been tested in mouse models. There have been issues with the development of liver tumours, insufficient target cells are reached and the therapy is not toxic enough to target cells. There are attempts underway to manufacture antitumour vaccines.In this technique Epstein-Barr virus vectors mediate gene transfer into human B lymphocytes.[7] Other areas of research include:

A recent trial, approved by the American Food and Drug Administration, is for the treatment of Parkinson's disease. This is a phase 1 clinical trial with 11 patients already enrolled. They are aiming to produce the neuroprotective and restorative subthalamic glutamic decarboxylase. There have been no adverse events reported to date.[13]

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Gene Therapy | Doctor | Patient.co.uk