Red Blood Cell Anchoring Enables Targeted Transduction and Re-Administration of AAV-Mediated Gene Therapy.

ABSTRACT: Adeno-associated virus (AAV)-mediated gene therapy is a promising therapeutic modality for curing many diseases including monogenic diseases. However, limited tissue-targeting and restricted re-administration due to the vector immunogenicity largely restrict its therapeutic potential. Here, using a red blood cell (RBC) as the carrier vehicle for AAV is demonstrated to improve its tissue-targeted transduction and enable its re-administration. Anchoring AAV to the RBC surface minimally affected its infectability toward endothelial cells. Meanwhile, AAV anchored onto RBCs is predominantly delivered to and shows efficient transduction in the lungs by virtue of the biophysical features of RBCs. RBC-anchored AAVs lead to a four- to five-fold enhancement in target gene expression in the lungsas c

SUBMITTER: Zhao Z 

PROVIDER: S-EPMC9404386 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature