Design, development, and evaluation of gene therapeutics specific to KSHV-associated diseases.

ABSTRACT: Kaposi sarcoma associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS) and two human B cell lymphoproliferative diseases. KSHV-encoded latency-associated nuclear antigen (LANA) is expressed in KSHV-infected cancer cells. Thus, LANA is an attractive target for therapeutic intervention for KSHV-associated diseases. Here, we devised a cancer gene therapy vector using the adeno-associated virus (AAV), which capitalizes on the LANA's function to maintain terminal repeat (TR)-containing circular genomes and the TR's enhancer function for KSHV-inducible gene promoters. By including two TR copies with a lytic inducible gene promoter (TR2-OriP), we prepared an AAV vector, which expresses an engineered thymidine kinase (TK) selectively in KSHV-infected cells. Ganciclovir (

SUBMITTER: Inagaki T 

PROVIDER: S-EPMC12481920 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature