Recent Progress in Genome Editing for Gene Therapy Applications: The French Perspective.
CRISPR/Cas9
HSCs
T cell
gene editing toxicity
gene therapy
genome editing
Journal
Human gene therapy
ISSN: 1557-7422
Titre abrégé: Hum Gene Ther
Pays: United States
ID NLM: 9008950
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
pubmed:
9
9
2021
medline:
1
2
2022
entrez:
8
9
2021
Statut:
ppublish
Résumé
Recent advances in genome editing tools, especially novel developments in the clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases (CRISPR/Cas9)-derived editing machinery, have revolutionized not only basic science but, importantly, also the gene therapy field. Their flexibility and ability to introduce precise modifications in the genome to disrupt or correct genes or insert expression cassettes in safe harbors in the genome underline their potential applications as a medicine of the future to cure many genetic diseases. In this review, we give an overview of the recent progress made by French researchers in the field of therapeutic genome editing, while putting their work in the general context of advances made in the field. We focus on recent hematopoietic stem cell gene editing strategies for blood diseases affecting the red blood cells or blood coagulation as well as lysosomal storage diseases. We report on a genome editing-based therapy for muscular dystrophy and the potency of T cell gene editing to increase anticancer activity of chimeric antigen receptor T cells to combat cancer. We will also discuss technical obstacles and side effects such as unwanted editing activity that need to be surmounted on the way toward a clinical implementation of genome editing. We propose here improvements developed today, including by French researchers to overcome the editing-related genotoxicity and improve editing precision by the use of novel recombinant nuclease-based systems such as nickases, base editors, and prime editors. Finally, a solution is proposed to resolve the cellular toxicity induced by the systems employed for gene editing machinery delivery.
Identifiants
pubmed: 34494480
doi: 10.1089/hum.2021.191
doi:
Substances chimiques
Endonucleases
EC 3.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM