Killing hiv-infected cells by transduction with an hiv protease-activated caspase-3 protein

ABSTRACT AT PRESENT, TREATMENT OF HIV INFECTION USES SMALL INHIBITORY MOLECULES THAT TARGET HIV PROTEASE; HOWEVER, THE EMERGENCE OF RESISTANT HIV STRAINS IS INCREASINGLY PROBLEMATIC. TO

CIRCUMVENT THIS, WE REPORT HERE A NEW 'TROJAN HORSE' STRATEGY TO KILL HIV-INFECTED CELLS BY EXPLOITING HIV PROTEASE. WE ENGINEERED A TRANSDUCING, MODIFIED, APOPTOSIS-PROMOTING

CASPASE-3 PROTEIN, TAT–CASP3, THAT SUBSTITUTES HIV PROTEOLYTIC CLEAVAGE SITES FOR ENDOGENOUS ONES AND EFFICIENTLY TRANSDUCES ABOUT 100% OF CELLS, BUT REMAINS INACTIVE IN UNINFECTED CELLS. IN

HIV-INFECTED CELLS, TAT–CASP3 BECOMES PROCESSED INTO AN ACTIVE FORM BY HIV PROTEASE, RESULTING IN APOPTOSIS OF THE INFECTED CELL. THIS STRATEGY COULD ALSO BE APPLIED TO OTHER PATHOGENS

ENCODING SPECIFIC PROTEASES, SUCH AS HEPATITIS C VIRUS, CYTOMEGALOVIRUS AND MALARIA. Access through your institution Buy or subscribe This is a preview of subscription content, access via

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* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS SELECTIVE CELL DEATH IN HIV-1-INFECTED CELLS BY DDX3 INHIBITORS

LEADS TO DEPLETION OF THE INDUCIBLE RESERVOIR Article Open access 30 April 2021 TARGETED SHOCK-AND-KILL HIV-1 GENE THERAPY APPROACH COMBINING CRISPR ACTIVATION, SUICIDE GENE TBID AND

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references ACKNOWLEDGEMENTS We thank E.S. Alnemri for the human Casp3 cDNA; K. Wang for help with DEVD-AFC reactions; Abbott Labs for Ritonavir; S. Horning for doing the TUNEL assays; and D.

Goldberg, C. Rice, S. Virgin and all the members of the Dowdy and Ratner labs for critical input. This work was supported by the N.I.H. (L.R.) and the Howard Hughes Medical Institute

(S.F.D.). S.F.D. is an Assistant Investigator of the Howard Hughes Medical Institute. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Departments of Pathology and Medicine, Howard Hughes

Medical Institute, Washington University School of Medicine, St. Louis , 63110, Missouri, USA Adita M. Vocero-Akbani, Natalie A. Lissy & Steven F. Dowdy * Division of Molecular Oncology,

Departments of Pathology and Medicine, Washington University School of Medicine, St. Louis , 63110, Missouri, USA Adita M. Vocero-Akbani, Nancy Vander Heyden, Natalie A. Lissy, Lee Ratner 

& Steven F. Dowdy Authors * Adita M. Vocero-Akbani View author publications You can also search for this author inPubMed Google Scholar * Nancy Vander Heyden View author publications You

can also search for this author inPubMed Google Scholar * Natalie A. Lissy View author publications You can also search for this author inPubMed Google Scholar * Lee Ratner View author

publications You can also search for this author inPubMed Google Scholar * Steven F. Dowdy View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to Steven F. Dowdy. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Vocero-Akbani, A., Heyden, N., Lissy, N. _et al._ Killing

HIV-infected cells by transduction with an HIV protease-activated caspase-3 protein. _Nat Med_ 5, 29–33 (1999). https://doi.org/10.1038/4710 Download citation * Received: 05 August 1998 *

Accepted: 11 November 1998 * Issue Date: January 1999 * DOI: https://doi.org/10.1038/4710 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get

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