The current price spurt of biotechnology leads me to think that something is brewing in the research. Biotech is a sector with tremendous asymmetric information. The market will move before the news makes sense… this story isn’t the mover of course, just another crispr story. But something is happening. I’m watching and waiting, once more on the wrong side of the asymmetrical info…
Over the last five years, the CRISPR gene editing system has revolutionized microbiology and renewed hopes that genetic engineering might eventually become a useful treatment for disease. But time has revealed the technology’s limitations. For one, gene therapy currently requires using a viral shell to serve as the delivery package for the therapeutic genetic material. The CRISPR molecule is simply too large to fit with multiple guide RNAs into the most popular and useful viral packaging system.
The new study from Farzan and colleagues helps solve this problem by letting scientists package multiple guide RNAs.
This advance could be important if gene therapy is to treat diseases such as hepatitis B, Farzan said. After infection, hepatitis B DNA sits in liver cells, slowly directing the production of new viruses, ultimately leading to liver damage, cirrhosis and even cancer. The improved CRISPR-Cpf1 system, with its ability to ‘multiplex,’ could more efficiently digest the viral DNA, before the liver is irrevocably damaged, he said.
“Efficiency is important. If you modify 25 cells in the liver, it is meaningless. But if you modify half the cells in the liver, that is powerful,” Farzan said. “There are other good cases—say muscular dystrophy—where if you can repair the gene in enough muscle cells, you can restore the muscle function.”
Two types of these molecular scissors are now being widely used for gene editing purposes: Cas9 and Cpf1. Farzan said he focused on Cpf1 because it is more precise in mammalian cells. The Cpf1 molecule they studied was sourced from two types of bacteria, Lachnospiraceae bacterium and Acidaminococus sp., whose activity has been previously studied in E. coli. A key property of these molecules is they are able to grab their guide RNAs out of a long string of such RNA; but it was not clear that it would work with RNA produced from mammalian cells. Guocai tested this idea by editing a firefly bioluminescence gene into the cell’s chromosome. The modified CRISPR-Cpf1 system worked as anticipated.
“This means we can use simpler delivery systems for directing the CRISPR effector protein plus guide RNAs,” Farzan said. “It’s going to make the CRISPR process more efficient for a variety of applications.”
Looking forward, Farzan said the Cpf1 protein needs to be more broadly understood so that its utility in delivering gene therapy vectors can be further expanded.