Overcoming innate immune barriers that impede AAV gene therapy vectors.
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
04 01 2021
04 01 2021
Historique:
entrez:
4
1
2021
pubmed:
5
1
2021
medline:
8
9
2021
Statut:
ppublish
Résumé
The field of gene therapy has made considerable progress over the past several years. Adeno-associated virus (AAV) vectors have emerged as promising and attractive tools for in vivo gene therapy. Despite the recent clinical successes achieved with recombinant AAVs (rAAVs) for therapeutics, host immune responses against the vector and transgene product have been observed in numerous preclinical and clinical studies. These outcomes have hampered the advancement of AAV gene therapies, preventing them from becoming fully viable and safe medicines. The human immune system is multidimensional and complex. Both the innate and adaptive arms of the immune system seem to play a concerted role in the response against rAAVs. While most efforts have been focused on the role of adaptive immunity and developing ways to overcome it, the innate immune system has also been found to have a critical function. Innate immunity not only mediates the initial response to the vector, but also primes the adaptive immune system to launch a more deleterious attack against the foreign vector. This Review highlights what is known about innate immune responses against rAAVs and discusses potential strategies to circumvent these pathways.
Identifiants
pubmed: 33393506
pii: 143780
doi: 10.1172/JCI143780
pmc: PMC7773343
doi:
pii:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : UG3 HL147367
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI067497
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141181
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI100263
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS076991
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI128358
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL097088
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI067497
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI136007
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL131471
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI149646
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI067497
Pays : United States
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