Gene therapy gets CRISPR

CRISPR technology allows gene editing
Image by By Hiroshi Nishimasu, F. Ann Ran, Patrick D. Hsu, Silvana Konermann, Soraya I. Shehata, Naoshi Dohmae, Ryuichiro Ishitani, Feng Zhang, and Osamu Nureki via Wikimedia Commons

Many people believe that the future of medicine lies in gene therapy: diagnosing and correcting the genetic defects which cause a disease. Until recently, this has been a pipe dream because available technologies have been too expensive and too inefficient to successfully treat human patients. But in the last two years that has radically changed.

Last year Illumina’s $1000 genome was much feted by the scientific community. Now it is possible to have your entire genome sequenced for only $1000. When you compare that to the average cost of X-rays ($150-250), or an abdominal ultrasound ($400), that looks like really good value. Of course whole genome sequencing gives a lot of data which is completely unintelligible to non-scientists. Lucky there are many companies swooping in to fill that newly made hole in the market.

This year the problem of cheap and accessible gene editing has been solved with CRISPR/Cas technology. CRISPR stands for the catchy name of ‘clustered regularly interspaced short palindromic repeats’. This translates to short repeat sequences of DNA. CRISPRs and CRISPR-associated (Cas) genes are part of the immune defense mechanism that bacteria use against viruses. Many of the Cas genes encode for DNA-cutting enzymes called nucleases. These enzymes only become activated when they bind to an RNA sequence called CRISPR RNA.

When bacteria are infected with viruses, some of the viral DNA is inserted into the bacteria’s DNA and this forms CRISPRs. The CRISPRs are a record of previous infections, so if the bacteria are infected again, they recognise the viral DNA, and can produce a CRISPR RNA sequence. This RNA guides a Cas nuclease to cut the viral DNA so that the virus can’t replicate. Genius.

Scientists really got excited when they realised they could adapt this system to target any DNA sequence. And, even better, to re-write any part of the genome. All they have to do is design a short RNA sequence, called a guide RNA, which tells a Cas nuclease (usually Cas9) to cut DNA in a particular place. Cas9 cuts both strands of the DNA molecule creating a double-stranded break. The cell can repair this break by a process called homology directed repair. This takes a template DNA sequence and copies it into the broken DNA.

So now scientists can identify a disease-causing mutation, cut out that mutation using Cas9, and replace it with the DNA sequence that would be there in a healthy person.

This is a great example of how funding basic research, in this case into bacterial immunity, can lead to a powerful medical breakthrough.

More info here.

The Scientific Review:
Sander and Joung. CRISPR-Cas systems for editing, regulating and targeting genomes. Nature Biotech. 2014

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