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CRISPR-Cas9-based Genome Engineering to Generate Jurkat Reporter Models for HIV-1 Infection with Selected Proviral Integration Sites
Published on: November 14, 2018
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HIV-1 cure strategies: why CRISPR?
Andrew J Atkins1,2, Alexander G Allen1,2, Will Dampier1,2
1Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA USA.
Expert Opinion on Biological Therapy
|December 17, 2020
Summary
HIV-1 cure research focuses on eliminating the latent reservoir. CRISPR/Cas9 proviral targeting directly removes integrated proviral DNA, offering a potential permanent solution to prevent viral rebound.
Area of Science:
- Virology
- Immunology
- Gene Therapy
Background:
- Antiretroviral therapy (ART) controls HIV-1 but requires lifelong adherence.
- Latent reservoirs of integrated proviral DNA drive viral rebound, necessitating curative strategies.
- Targeting the latent reservoir is crucial for achieving a functional HIV-1 cure.
Purpose of the Study:
- To review current strategies for developing curative HIV-1 therapies.
- To emphasize the potential of CRISPR/Cas9 gene editing for HIV-1 eradication.
- To discuss recent advances and future directions in HIV-1 cure research.
Main Methods:
- Review of existing HIV-1 cure strategies including shock and kill, broadly neutralizing antibodies (bNAbs), block and lock, CAR T cells, and immune checkpoint modulation.
- Detailed examination of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) based approaches.
- Focus on CRISPR/Cas9 for coreceptor ablation and proviral excision/inactivation.
Main Results:
- Various strategies show promise for curative or adjuvant HIV-1 therapies.
- CRISPR/Cas9 proviral targeting directly addresses integrated proviral DNA.
- This approach does not require an innate or adaptive immune response for efficacy.
Conclusions:
- CRISPR/Cas9 gene editing offers a unique strategy to permanently eliminate the source of HIV-1 resurgence.
- Targeting integrated proviral DNA is a key step towards a functional HIV-1 cure.
- Further research and translation are needed to develop effective CRISPR/Cas9-based HIV-1 therapeutics.
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