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gene editing

Indications: - germline editing on human embryos & gametes to facilitate research on the possible future clinical applications [3] - TTR mRNA-guided CRISPR-Cas9 system with durable knockout of TTR in 6 patients with transthyretin amyloidosis after a single dose [5] - germline editing CRISPR-Casgevy system FDA-approved for treatment of sickle-cell disease* [6] - CRISPR-Cas9 system for treatment of beta-thalassemia [7] - high hopes for familial Alzheimer's disease [7] Contraindications: - germline gene editing that ends in a human pregnancy [3] - clinical use without compelling medical rationale, evidence of benefit & ethical justification [3] Comparative biology: - CRISPR can selectively knock out a single target gene in living mice

Related

CRISPR; clustered regularly interspaced short palindromic repeats RNA editing

Specific

lovotibeglogene autotemcel (Lyfgenia)

General

genome editing

References

  1. Ding Q et al Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res 2014 Jun 10 PMID: 24916110 http://circres.ahajournals.org/content/early/2014/06/10/CIRCRESAHA.115.304351
  2. Human Genome Editing. Science, Ethics, and Governance Committee on Human Gene Editing. Scientific,Medical, and Ethical Considerations. A Report of the National Acadey of Sciences and National Academy of Medicine. 2017 https://www.nap.edu/read/24623/chapter/1 - The National Academy of Science, Engineering, Medicine. News Release. Feb 14, 2017 With Stringent Oversight, Heritable Germline Editing Clinical Trials Could One Day Be Permitted for Serious Conditions: Non-Heritable Clinical Trials should Be Limited to Treating or Preventing Disease or Disability at This Time. http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=24623&_ga=1.204246480.1184730628.1487090016
  3. Ormond KE, Mortlock DP, Scholes DT et al ASHG Position Statement. Human Germline Genome Editing. Am J Human Genetics. vol 101, Issue 2, p167-176. Aug 3, 2017 PMID: 28777929 http://www.cell.com/ajhg/fulltext/S0002-9297(17)30247-1 - American Society of Human Genetics. News Release. Aug 3, 2017 11 Organizations Urge Cautious but Proactive Approach to Gene Editing. Medical, Research, and Counseling Groups Issue Statement on Germline Genome Editing. http://www.ashg.org/press/201708-genome-editing.shtml
  4. Church G Compelling Reasons for Repairing Human Germlines. N Engl J Med 2017; 377:1909-1911. November 16, 2017 DOI: 10.1056/NEJMp1710370 http://www.nejm.org/doi/full/10.1056/NEJMp1710370 - Cwik B. Designing Ethical Trials of Germline Gene Editing. N Engl J Med 2017; 377:1911-1913. November 16, 2017 PMID: 29141166 http://www.nejm.org/doi/full/10.1056/NEJMp1711000
  5. George J In a First, CRISPR Infusion Edits Genes Directly in Humans. "A watershed moment in modern medicine," says genetics expert. MedPage Today June 28, 2021 https://www.medpagetoday.com/neurology/generalneurology/93314 - Gillmore JD, Gane E, Taubel J et al CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med 2021. June 26 PMID: 34215024 https://www.nejm.org/doi/full/10.1056/NEJMoa2107454
  6. AMA Morning Rounds. Dec 11, 2023 American Medical Association - Lou N Milestone Gene Therapies for Sickle Cell Disease Greenlit by FDA. Casgevy and Lyfgenia approved for one-time treatment of sickle cell disease. MedPage Today December 8, 2023 https://www.medpagetoday.com/hematologyoncology/hematology/107751 - Brooks PJ, Clay JP A Closer Look at the Approval of CRISPR/Cas9 Gene Therapy for Sickle Cell Disease. This landmark event brings up broader considerations and implications for other diseases. MedPage Today. Dec 11, 2023 https://www.medpagetoday.com/opinion/second-opinions/107793 - 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
  7. Thompson T How CRISPR gene editing could help treat Alzheimer's. Some researchers hoping that gene-editing technology can conquer forms of Alzheimer's caused by genetic mutations. Nature News. Dec 11 2023 https://www.nature.com/articles/d41586-023-03931-5