CRISPR @MIT
Curator & Reporter: Aviva Lev-Ari, PhD, RN
FIRST, there was Jennifer A. Doudna @ Berkeley
Along with colleagues at UC Berkeley and in Sweden, Doudna, in 2012, discovered a gene-editing technique called CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). The technology “gives researchers the equivalent of a molecular surgery kit for routinely disabling, activating or changing genes,” wrote Science magazine in a Dec. 2013 article naming CRISPR one of its runners-up for breakthrough of the year. CRISPR “has become red hot in the past year,” the journal article said.
New DNA-editing technology spawns bold UC initiative
At the core of the initiative is a revolutionary technology discovered two years ago at UC Berkeley by Jennifer A. Doudna, executive director of the initiative and the new faculty chair. The technology, precision “DNA scissors” referred to as CRISPR/Cas9, has exploded in popularity since it was first published in June 2012 and is at the heart of at least three start-ups and several heavily-attended international meetings. Scientists have referred to it as the “holy grail” of genetic engineering and a “jaw-dropping” breakthrough in the fight against genetic disease. In honor of her discovery and earlier work on RNA, Doudna received last month the Lurie Prize of the Foundation for the National Institutes of Health.
“Professor Doudna’s breakthrough discovery in genomic editing is leading us into a new era of possibilities that we could have never before imagined,” said Li Ka-shing, chairman of the Li Ka Shing Foundation. “It is a great privilege for my foundation to engage with two world-class public institutions to launch the Innovative Genomics Initiative in this quest for the holy grail to fight genetic diseases.”
Ribozymes and RNA Machines – Work of Jennifer A. Doudna
Gene Therapy and the Genetic Study of Disease: @Berkeley and @UCSF – New DNA-editing technology spawns bold UC initiative as Crispr Goes Global
Evaluate your Cas9 Gene Editing Vectors: CRISPR/Cas Mediated Genome Engineering – Is your CRISPR gRNA optimized for your cell lines?
CRISPR-Cas: A powerful new tool for precise genetic engineering
THEN, there was development of CRISPR Applications @MIT using a precise way to delete and edit specific bits of DNA—even by changing a single base pair. This means they can rewrite the human genome at will.
Genome Surgery
Over the last decade, as DNA-sequencing technology has grown ever faster and cheaper, our understanding of the human genome has increased accordingly. Yet scientists have until recently remained largely ham-fisted when they’ve tried to directly modify genes in a living cell. Take sickle-cell anemia, for example. A debilitating and often deadly disease, it is caused by a mutation in just one of a patient’s three billion DNA base pairs. Even though this genetic error is simple and well studied, researchers are helpless to correct it and halt its devastating effects.
Now there is hope in the form of new genome-engineering tools, particularly one called CRISPR. This technology could allow researchers to perform microsurgery on genes, precisely and easily changing a DNA sequence at exact locations on a chromosome. Along with a technique called TALENs, invented several years ago, and a slightly older predecessor based on molecules called zinc finger nucleases, CRISPR could make gene therapies more broadly applicable, providing remedies for simple genetic disorders like sickle-cell anemia and eventually even leading to cures for more complex diseases involving multiple genes. Most conventional gene therapies crudely place new genetic material at a random location in the cell and can only add a gene. In contrast, CRISPR and the other new tools also give scientists a precise way to delete and edit specific bits of DNA—even by changing a single base pair. This means they can rewrite the human genome at will.
original article in Technology Review
http://www.technologyreview.com/review/524451/genome-surgery/
COMMENTS
This is of course fascinating. Every time I read an article about such work, I hope that it’s an early sign of life-changing breakthroughs at the clinical level for people like my developmentally disabled son.
Unfortunately, as the years pass I continue to find an enormous gulf between reports of what might be coming and what is actually available. I’ve contacted researchers only to learn that their research is hurting for money and going nowhere fast. I’ve gone to prominent practitioners and found it impossible even to get a blood draw.
It’s wonderful that people are pursuing this research, but somehow progress, if it occurs, needs to find expression out in the world. http://www.fatherspledge.com/seeking-resolution.php
@fatherspledge Thank you for your comment – very moving even I do not know you. The problem with such a disrupting research is, that it is further away than “optimists” think it is and that is much nearer than “pesimists” belive it is. I personally think this is a throughbrough I have never read about in the last 15 years or so and estimate that it will take a decade or two before it is broadly available – sorry – but that is my estimate only and could be wrong in both dimensions but I am in the optimistic camp and think this is a real game changer – appologies for not finding better expressions.
I’m on the edge of my seat reading this. Absolutely fantastic article. It’s a great time to be alive.
The advances in our genomic understanding and tools over the proceeding decade have been incredible and I am always excited to read articles such as this one. I hope that the field maintains its momentum and continues to see modest increases in velocity. Keeping in mind that with great power comes great responsibility, I hope that the discussion is already occurring on how to utilize these tools to minimize the threats of improper use, but I trust the benefits will greatly outweigh any dangers. Great article!
Fantastic article – thank you. I would suggest it should be added to the “Best American Science and Natural Writing 2014” anthology, btw.
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This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.
This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.