Despite the fact that the therapeutic utility of CRISPR-based
approaches has yet to be demonstrated, venture dollars keep flowing into new
companies developing the platform. But proof of concept may come faster than
expected as new findings show that a CRIPSR-based compound can correct a
mutation in adult mice with genetic liver disease.1
and his team have now for the first time used CRISPR-Cas9 therapeutically. The
researchers chose tyrosinemia type I for their proof-of-concept studies.
Delivery and off-target activity are still the primary
challenges for any CRISPR-Cas9-based therapeutics. Indeed, the authors of the
new paper acknowledged that they stacked the deck in their favor- choosing a
disease of the liver, in which delivery is less of a challenge and
high-efficiency editing is not necessary to alter the disease.
to Krieg, pursuing ex vivo applications with the editing platform looks
to be the best strategy for the short term.
Donner, A. SciBX 7(16);
doi:10.1038/scibx.2014.447 Published online April 24, 2014
1. Yin, H. et
al. Nat. Biotechnol.; published online March 30, 2014;
Contact: Daniel G. Anderson, Massachusetts Institute of Technology,
Cambridge, Mass. e-mail: firstname.lastname@example.org
2. Mali, P. et al. Science 339, 823-826 (2013)
3. Cong, L. et al. Science 339, 819-823 (2013)
4. Cho, S.W. et al. Nat. Biotechnol.
31, 230-232 (2013)
5. Hwang, W.Y. et al. Nat. Biotechnol.
31, 227-229 (2013)
6. Jiang, W. et al. Nat. Biotechnol.
31, 233-239 (2013)
7. Jinek, M. et al. eLife 2,
e00471; published online Jan. 29, 2013; doi:10.7552/eLife.00471
8. Wang, H. et al. Cell 153, 910-918 (2013)
9. Niu, Y. et al. Cell 156, 836-843 (2014)
10. Yang, H. et al. Cell 154, 1370-1379 (2013)
11. Cain, C. SciBX 6(19);
12. Cain, C. SciBX 6(4);
13. Fu, Y. et al. Nat. Biotechnol. 31, 822-826 (2013)
14. Hsu, P.D. et al. Nat. Biotechnol.
31, 827-832 (2013)
15. Mali, P. et al. Nat. Biotechnol.
31, 833-838 (2013)
16. Paulk, N.K. et al. Hepatology 51, 1200-1208 (2010)
AND INSTITUTIONS MENTIONED
Alnylam Pharmaceuticals Inc. (NASDAQ: ALNY), Cambridge, Mass.
Broad Institute of MIT and Harvard, Cambridge, Mass.
Caribou Biosciences Inc., Berkeley Calif.
CRISPR Therapeutics, Basel, Switzerland
The David H. Koch Institute for Integrative Cancer Research
at MIT, Cambridge, Mass.
Hannover Medical School, Hannover, Germany
Harvard University, Cambridge, Mass.
Helmholtz Centre for Infection Research, Braunschweig, Germany
Howard Hughes Medical Institute, Chevy Chase, Md.
Lawrence Berkeley National Laboratory, Berkeley, Calif.
Massachusetts General Hospital, Boston, Mass.
Massachusetts Institute of Technology, Cambridge, Mass.
McGovern Institute for Brain Research at MIT, Cambridge, Mass.
Oregon Health & Science University, Beaverton, Ore.
(NYSE:PFE), New York, N.Y.
RaNA Therapeutics Inc., Cambridge, Mass.
Sarepta Therapeutics Inc. (NASDAQ:SRPT), Cambridge, Mass.
Skolkovo Institute of Science and Technology, Skolkovo, Russia
Stanford University School of Medicine, Stanford, Calif.
University of California, Berkeley, Calif.
University of Massachusetts Medical School, Worcester, Mass.
San Francisco, Calif.