Fig. 1: Illustration of the HIV-1 specific targeted shock-and-kill approach with CRISPRa and tBid delivered by CD3-retargeted adenoviruses. | Gene Therapy

Fig. 1: Illustration of the HIV-1 specific targeted shock-and-kill approach with CRISPRa and tBid delivered by CD3-retargeted adenoviruses.

From: Targeted shock-and-kill HIV-1 gene therapy approach combining CRISPR activation, suicide gene tBid and retargeted adenovirus delivery

Fig. 1: Illustration of the HIV-1 specific targeted shock-and-kill approach with CRISPRa and tBid delivered by CD3-retargeted adenoviruses.The alt text for this image may have been generated using AI.

Adenovirus vectors ensure effective delivery of the HIV-1 specific CRISPRa shock or HIV-1 specific tBid suicide kill strategies. Moreover, coating of Ads with CD3-retargeting adapters provides a high level of T cell specific delivery. The dCas9-VPR and the HIV-1 specific gRNA-V in the shock Ad-CRISPRa-V activate expression of latent provirus by targeting the HIV-1 LTR promoter. Expression of early genes tat and rev leads to activation of the tBid suicide vector delivered by the kill Ad-tBid. The Tat protein binds to the HIV-1 LTR promoter driving expression of the tBid suicide gene, and the Rev protein binds to the Rev-responsive element (RRE) in the tBid mRNA enabling export of this mRNA to the cytoplasm. Expression of the tBid protein induces apoptosis very rapidly within 24 h since very low tBid protein amounts suffice to induce release of cytochrome c (Cyt c) and lead to mitochondrial outer membrane permeabilization (MOMP). Figure created with BioRender.com (Figure publication license HO24KAK4FD).

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