Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells.

ABSTRACT:

Background

Patients with T-cell immunodeficiencies are generally treated with allogeneic hematopoietic stem cell transplantation, but alternatives are needed for patients without matched donors. An innovative intrathymic gene therapy approach that directly targets the thymus might improve outcomes.

Objective

We sought to determine the efficacy of intrathymic adeno-associated virus (AAV) serotypes to transduce thymocyte subsets and correct the T-cell immunodeficiency in a zeta-associated protein of 70 kDa (ZAP-70)-deficient murine model.

Methods

AAV serotypes were injected intrathymically into wild-type mice, and gene transfer efficiency was monitored. ZAP-70^-/- mice were intrathymically injected with an AAV8 vector harboring the ZAP70 gene. Thymus structure

SUBMITTER: Pouzolles M 

PROVIDER: S-EPMC8287836 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature