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CRISPR; clustered regularly interspaced short palindromic repeats

may play role in RNA interference &/or gene editing Indications: - useful for identifying molecular targets for treatment of disease [1] - mutated MYBPC3 successfully edited in human embryos [8] Principle: - CRISPR-associated system Cas - components include - adeno-associated virus delivery vehicle - gene targeting - gene-cleavage - oligonucleotides to act as a repair template (Cas) ? - result is reduction in gene expression vs reduction in mRNA translation vs reduced production of defective protein - CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. [14] Notes: - a version of CRISPR that allows selective activation of several specific genes at once is described [3] - off-target effects (i.e. genes other than targeted gene) may occur [4] - newer technique reduces or eliminates off-target effects [6] Comparative biology: - CRISPR gene editing effective in Duchenne muscular dystrophy in mice [5]

Related

gene editing RNA interference; clustered regularly interspaced short palindromic repeats (CRISPR)

Specific

exagamglogene autotemcel (Casgevy)

General

biochemistry molecular diagnostic test

References

  1. Wang T et al. Genetic screens in human cells using the CRISPR-Cas9 system. Science 2014 Jan 3; 343:80 PMID: 24336569 http://www.sciencemag.org/content/343/6166/80 - Shalem O et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 2014 Jan 3; 343:84. PMID: 24336571 http://www.sciencemag.org/content/343/6166/84
  2. Niu Y et al. Generation of gene-modified cynomolgus monkey via Cas9/RNA- mediated gene targeting in one-cell embryos. Cell 2014 Jan 30; PMID: 24486104 http://www.cell.com/retrieve/pii/S0092867414000798 - Pennisi E. Transgenic animals. Editing of targeted genes proved possible in monkeys. Science 2014 Jan 31; 343:476 PMID: 24482459
  3. Konermann S et al. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 2015 Jan 29; 517:583. PMID: 25494202 - Cho SW and Chang HY. CRISPR engineering turns on genes. Nature 2015 Jan 29; 517:560 PMID: 25631441
  4. Ran FA et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 2015 Apr 9; 520:186. PMID: 25830891 - Liang P et al. CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein Cell 2015 May; 6:363. PMID: 25894090 - Baltimore D et al. A prudent path forward for genomic engineering and germline gene modification. Science 2015 Apr; 348:36. PMID: 25791083
  5. Nelson CE, Hakim CH, Ousterout DG et al In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science. 2016 Jan 22;351(6271):403-7 PMID: 26721684 http://science.sciencemag.org/content/351/6271/403 - Long C, Amoasii L, Mireault AA Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science. 2016 Jan 22;351(6271):400-3 PMID: 26721683 Free PMC Article http://science.sciencemag.org/content/351/6271/400 - Tabebordbar M, Zhu K, Cheng JK In vivo gene editing in dystrophic mouse muscle and muscle stem cells. Science. 2016 Jan 22;351(6271):407-11 PMID: 26721686 http://science.sciencemag.org/content/351/6271/407
  6. Kleinstiver BP, Pattanayak V, Prew MS et al. High-fidelity CRISPR-Cas9 nucleases with no detectable genome- wide off-target effects. Nature 2016 Jan 28; 529:490 PMID: 26735016
  7. Calos MP The CRISPR Way to Think about Duchene's N Engl J Med 2016; 374:1684-1686. April 28, 2016 PMID: 27119241 http://www.nejm.org/doi/full/10.1056/NEJMcibr1601383
  8. Ma H, Marti-Gutierrez N, Park SW et al Correction of a pathogenic gene mutation in human embryos. Nature (2017). Published online 02 August 2017 PMID: 28783728 http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23305.html
  9. Komaroff AL Gene Editing Using CRISPR. Why the Excitement? JAMA. Published online August 10, 2017 PMID: 28796848 http://jamanetwork.com/journals/jama/fullarticle/2646800
  10. Cong L, Ran FA, Cox D et al Multiplex genome engineering using CRISPR/Cas systems. Science. 2013 Feb 15;339(6121):819-23. Epub 2013 Jan 3. PMID: 23287718 Free PMC Article
  11. Mali P, Yang L, Esvelt KM et al RNA-guided human genome engineering via Cas9. Science. 2013 Feb 15;339(6121):823-6. Epub 2013 Jan 3. PMID: 23287722 Free PMC Article
  12. Gootenberg JS, Abudayyeh OO, Lee JW et al Nucleic acid detection with CRISPR-Cas13a/C2c2. Science. 2017 Apr 28;356(6336):438-442. Epub 2017 Apr 13. PMID: 28408723 Free PMC Article
  13. Chen ZH, Yu YP, Zuo ZH et al Targeting genomic rearrangements in tumor cells through Cas9- mediated insertion of a suicide gene. Nat Biotechnol. 2017 Jun;35(6):543-550. Epub 2017 May 1. PMID: 28459452
  14. FDA News Release, Dec 8, 2023 FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease