A new team at Medical College of Georgia is taking aim at defective gene sequences that cause disease using the revolutionary CRISPR method that allows precise editing of specific sequences to create animal models of those diseases.

Drs. Lin Gan and Joseph Miano sit at a conference table outside their new lab at Augusta University, and in the blink of an eye the discussion goes from how they began using a certain technology in its early days of 2013 to how they are applying the latest iteration that came out only last month.

Thats how fast they, and their field of genome editing and manipulation, are moving.

Gan and Miano and colleague Xiaochun Long were recently recruited as a team to the Medical College of Georgia at AU, where Gan became the founding director of the Transgenic and Genome Editing Core. He is a Georgia Research Alliance Eminent Scholar in Neuroscience, and Miano is a J. Harold Harrison Distinguished University Chair in Vascular Biology.

The floor of their lab shows they are only a few months into the new stint in Augusta.

Were still living out of boxes, Miano said as he stepped around cardboard boxes.

The two have been together since the early 1990s in Houston and spent the past 20 years working together at the University of Rochester, though they had no idea they were both headed there initially.

Unbeknownst to me, he was being recruited at the same time, Miano said.

Were meant to be together and we didnt even coordinate our move, Gan said jokingly.

The move to Augusta was deliberate. Miano had interviewed at MCG in 1995 and wanted no part of it then and was not interested again after recently giving a talk at the school and receiving some initial offers.

But then I came down for a second visit and I thought, Hmm, this is interesting, Miano said. They have really built it up well. Theres an opportunity here to make a difference.

But the three were a package deal Long and Miano are now married, and Gan would not have come without them.

I also see this as an opportunity, Gan said. I can definitely have more support here for the Core.

He was quite familiar with MCG and in particular the eye researchers there, which is also an interest for him.

There is a very strong eye group here, Gan said, and he has been supplying them with animal models of disease for more than a decade. Creating those animals models, where a gene may be knocked out or silenced, got a lot easier for him with the advent of CRISPR, or clustered regularly interspaced short palindromic repeats.

It is the ability to take a short length of genetic material known as a guide RNA, which will match up with a highly specific target in DNA and in many instances attach an enzyme that then precisely cuts the DNA at that spot, allowing researchers to target very specific sections of that DNA and either silence genes or in some cases begin the replacement of defective sections.

Gan and Miano use CRISPR to create animal models in mice of human disease that other researchers can use to study those diseases. They often involve a small mutation in the genetic material that gives rise to the condition, known as a single nucleotide polymorphism or SNP.

CRISPR is very effective for SNPs, for mutations, Gan said. It is a little quicker.

There are a lot of them, and more are being added all of the time, Miano said.

The latest database of SNPs, that last time I looked was over 600 million, he said.

Miano was at the conference in 2012 when Dr. Jennifer Doudna of the University of California, Berkley made what he called a jaw-dropping revelation that a bacterial defense system against viruses allows for the precise targeting and cutting of DNA. CRISPR soon became a hot new technique that he and Gan adopted the following year.

Though they are primarily working in mice, CRISPR can be used in other animal models and outside the field as well, Miano said.

I think what is exciting, as Lin says, anything with a genome can be edited, he said. The agricultural field is blowing up. There are all kinds of stuff going on in agriculture with editing.

It has already reached the human level. The National Library of Medicines database of clinical trials involving CRISPR-aided therapy or testing lists 20 active studies, although only a handful are in the U.S. and most are in China. Therapies are most likely to focus first on what Miano called the low-hanging fruit, the 7,000 or so diseases that arise from a single gene defect, such as cystic fibrosis.

More complex conditions, such as heart disease, are going to be tough, he said.

There is no silver bullet for those, but CRISPR will be at the center of that work, he said.

For his part, Gan would like to focus on the eye. The tissue there is thinner and more concentrated, so correcting a defect in vision in, for instance, the macular area of the retina at the back of the eye involves manipulating much fewer cells than trying to correct something in the brain or elsewhere.

This is great for manipulation because a lot of our vision comes from the macular region, Gan said. Its a very small region. That is why he believes in terms of therapies, the eye will be one of the first.

See the article here:
Genome editing heralds new era of disease research, therapy - The Augusta Chronicle

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