Unknown

Dataset Information

0

Exosome-mediated stable epigenetic repression of HIV-1.


ABSTRACT: Human Immunodeficiency Virus (HIV-1) produces a persistent latent infection. Control of HIV-1 using combination antiretroviral therapy (cART) comes at the cost of life-shortening side effects and development of drug-resistant HIV-1. An ideal and safer therapy should be deliverable in vivo and target the stable epigenetic repression of the virus, inducing a stable "block and lock" of virus expression. Towards this goal, we developed an HIV-1 promoter-targeting Zinc Finger Protein (ZFP-362) fused to active domains of DNA methyltransferase 3 A to induce long-term stable epigenetic repression of HIV-1. Cells were engineered to produce exosomes packaged with RNAs encoding this HIV-1 repressor protein. We find here that the repressor loaded anti-HIV-1 exosomes suppress virus expression and that this suppression is mechanistically driven by DNA methylation of HIV-1 in humanized NSG mouse models. The observations presented here pave the way for an exosome-mediated systemic delivery platform of therapeutic cargo to epigenetically repress HIV-1 infection.

SUBMITTER: Shrivastava S 

PROVIDER: S-EPMC8452652 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6019856 | biostudies-other
| S-EPMC8507954 | biostudies-literature
| S-ECPF-GEOD-21068 | biostudies-other
| S-EPMC4703871 | biostudies-literature
| S-EPMC2877570 | biostudies-literature
| S-EPMC3931505 | biostudies-literature
| S-EPMC3434655 | biostudies-literature
| S-EPMC5749160 | biostudies-literature
| S-EPMC3204918 | biostudies-literature
| S-EPMC4701980 | biostudies-literature