Combination gene therapy for HIV using a conditional suicidal gene with CCR5 knockout.

ABSTRACT:

Background

Gene therapy approaches using hematopoietic stem cells to generate an HIV resistant immune system have been shown to be successful. The deletion of HIV co-receptor CCR5 remains a viable strategy although co-receptor switching to CXCR4 remains a major pitfall. To overcome this, we designed a dual gene therapy strategy that incorporates a conditional suicide gene and CCR5 knockout (KO) to overcome the limitations of CCR5 KO alone.

Methods

A two-vector system was designed that included an integrating lentiviral vector that expresses a HIV Tat dependent Thymidine Kinase mutant SR39 (TK-SR39) and GFP reporter gene. The second non-integrating lentiviral (NIL) vector expresses a CCR5gRNA-CRISPR/Cas9 cassette and HIV Tat protein.

Results

Transduction of cells seque

SUBMITTER: Mehmetoglu-Gurbuz T 

PROVIDER: S-EPMC7847599 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature