Preprint Review Version 1 This version is not peer-reviewed

HIV-1: Tackling the Obstacles, Which Limit the Effectiveness of the CRISPR-Cas9 Gene Editing of the T Cell Co-Receptor, CCR5

Version 1 : Received: 17 July 2019 / Approved: 18 July 2019 / Online: 18 July 2019 (09:51:34 CEST)

How to cite: Hillman, T. HIV-1: Tackling the Obstacles, Which Limit the Effectiveness of the CRISPR-Cas9 Gene Editing of the T Cell Co-Receptor, CCR5 . Preprints 2019, 2019070211 (doi: 10.20944/preprints201907.0211.v1). Hillman, T. HIV-1: Tackling the Obstacles, Which Limit the Effectiveness of the CRISPR-Cas9 Gene Editing of the T Cell Co-Receptor, CCR5 . Preprints 2019, 2019070211 (doi: 10.20944/preprints201907.0211.v1).

Abstract

HIV-1 is a complicated and perplexing virus. It infects T cells, reverse transcribes its RNA into DNA, utilizes its host DNA machinery to replicate its HIV-DNA, translates the HIV-DNA into proteins, assembles itself for a budding escape from the T cell, and rapidly mutates its conformation. Partially, due to its complexity, there remains no cure for HIV or AIDs. However, recently with the discovery of TALENs, the use of Zinc fingers, and most of all the application of CRISPR-Cas9 technology, has given researchers a new hope in finding alternative gene therapies and treatments for diseases. With more focus on CRISPR-Cas9, this new and novel technology uses a guiding RNA, sgRNA, to lead a Cas9 nuclease to its target for deletion or to change that DNA site. The CRISPR-Cas9 can delete point mutations and multiple DNA sites. Because CRISPR can alter DNA sequences, several scientists have conducted research into CRISPR possibly curing more diseases as cancer, diabetes, and even HIV. HIV-1 drew the focus of a researcher named Dr. Ebina in 2013 when he was the first to design and apply CRISPR-Cas9 to genes found in the binding sites of the HIV-1, inhibiting HIV-1 gene expression. Since 2013 several other researchers have blocked HIV replication and infection through the CRISPR-Cas9 targeting the receptors of T cells called the CC chemokine receptor 5 or CCR5. HIV-1 binds to the CD4 receptor of T cells that consists of co-receptors CCR5 and CXCR4. If CCR5 expression can be removed, the HIV virus can not bind to T-cells, blocking the initial attachment stage, discontinuing the infection. However, there remain obstacles and issues for the CRISPR deletion of CCR5 for treating HIV-1. The issues include: 1) finding new and safe methods of CRISPR-Cas9 delivery, 2) clearing the latent HIV reservoirs, 3) improve the sgRNA design to avoid off-target mutations or deletions, and 4) effectively analyze the viral escape of HIV from CRISPR-Cas9 modifications. Therefore, the purpose of this review is to discuss possible techniques for removing the obstacles that can lessen the potential of CRISPR to delete CCR5, repressing HIV-1 into long-term remission.

Subject Areas

HIV-1; CRISPR-Cas9; T-cells; lipid nanoparticles; gut-associated-lymphoid tissue; Co-receptors; Probiotics; GI Tract,; Gene Editing

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.