Advancing gene-editing platforms to improve the viability of rare-disease therapeutics: key insights from a 2024 Scientific Exchange hosted by ARM, ISCT, and Danaher
Rare-disease therapeutics face viability challenges due to small patient populations and drug-development and regulatory frameworks that were not developed to address rapidly progressive or quickly fatal conditions. Because the majority of rare diseases are genetic in nature, gene-editing modalities offer substantial promise. This Scientific Exchange, co-hosted by the Alliance for Regenerative Medicine, the International Society for Cell and Gene Therapy, and Danaher Corporation in November 2024, set out to address the challenge of realizing the full promise of gene editing for rare-disease therapies by advancing platforms that leverage stable and reusable processes or components to develop multiple therapies. Through multi-stakeholder engagement and discussions of case studies in CRISPR/Cas nuclease, base, and prime editing, 4 key opportunities emerged that deliver value by holding platform elements constant and/or streamlining development steps: (1) consistent delivery vehicle; (2) consistent manufacturing; (3) benefit-risk appropriate quality requirements; and (4) expansive clinical trial designs. Together, these opportunities could yield up to 5-fold efficiency gains and result in substantial value creation for patients, regulators, and developers, potentially decreasing the time required to dose patients with a new gene-editing therapy from years down to 6 months.
Authors
- Harry L. Malech (ORCID: https://orcid.org/0000-0001-5874-5775)
- Josephine Lembong (ORCID: https://orcid.org/0000-0003-4124-782X)
- Ann Y. Lee (ORCID: https://orcid.org/0000-0002-8143-2635)
- Fyodor D. Urnov (ORCID: https://orcid.org/0000-0001-7542-4084)
- Nicholas Gertler
- Julianne Bruno
- Kiran Musunuru (ORCID: https://orcid.org/0000-0003-3298-0368)
- Pam Stetkiewicz
- Matt Diver
- Sadik H. Kassim
- Luis Barrera (ORCID: https://orcid.org/0000-0003-0612-6416)
- Matthew Hewitt (ORCID: https://orcid.org/0000-0001-8915-1996)
- David R. Liu (ORCID: https://orcid.org/0000-0002-9943-7557)
- Troy Lister
- Felix Grignon
- Audrey N. Le
- Lindsay Gasch
- Michael Lehmicke
- Vanessa Almendro-Navarro
Institutions
- Broad Institute (US)
- National Institutes of Health (US)
- Danaher (United States) (US)
- White Ribbon Alliance (US)
- Banner Wyoming Medical Center (US)
- Innovative Genomics Institute (US)
- Raptamer Discovery Group (United States) (US)
- Verve Therapeutics (United States) (US)
- Charles River Laboratories (United States) (US)
- National Institute of Allergy and Infectious Diseases (US)
- Fidelity Biosciences (United States) (US)
- Global Alliance for Regenerative Medicine (HN)
- AtlantiCare (US)
- CRISPR Therapeutics (Switzerland) (CH)
- International Society for Cellular Therapy (CA)
- Beam Therapeutics (United States) (US)
- University of Pennsylvania (US)
- University of California, Berkeley (US)
Publication Details
- Journal
- Cytotherapy
- Published
- 2025-06-24
- DOI
- https://doi.org/10.1016/j.jcyt.2025.06.010
- Citations
- 4
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 3.22