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An Efficient Gene Editing System to Tag and Isolate HIV-Infected Cells

  • Stage: Preclinical in vitro
  • Type: Diagnostic
  • Categories: Protein / Peptide

Technology Overview

HIV can persist in a latent state for decades within human immune cells despite life-sustaining advances in modern anti-retroviral therapy (ART). Current standard of care treatment reduces viral loads and improves outcomes of those living with HIV, but has no effect on latently infected cells which provide a life-long reservoir of infectious virions. These latently infected cells pose the greatest challenge to curing HIV, but account for as little as 0.003% of peripheral blood cells. To overcome the challenge posed by the scarcity of these cells in patients, genetic engineers at Fred Hutch have developed a method for tag-and-target isolation of latently infected cells. Dr. Jerome and his team use CRISPR/Cas9-based homology-independent target insertion (HITI) together with a reporter lacking a polyA signal to label HIV provirus in viable immune cells, and virtually eliminate off-target background noise. This breakthrough paves the way for vital research of latent viral infection and sets the stage for curative therapeutic development.

Applications

  • Analysis of provirus integration dynamics, T cell preference, and viral reactivation mechanics
  • Targeting and isolation of non-HIV proviruses (e.g., HTLV and HERVs)
  • Tagging of rare blood cells with off-target noise reduction

Advantages

  • Unmasks low abundance cells from blood (e.g., circulating tumor cells)
  • HITI requires no sequence homology for genetic editing which overcomes the difficulty of sequence variability inherent to HIV

Patent Information

Patent pending

Market Overview

The global HIV drug market was valued at $25.3 billion in 2018 and is expected to grow to $40.7 billion by 2026 giving a CAGR of 6.1%. ART is currently the major market driver for HIV/AIDS treatment. While ART reduces disease burden and improves patient outcomes, a curative treatment targeting latent infection is still an unmet need for the nearly 40 million patients living with HIV.

Investigator Overview

  • Keith Jerome, MD, PhD - Vaccine and Infectious Disease Division
Tech ID: 18-082
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