# Novel hematopoietic stem cell engineering and transplantation approaches for HIV cure

> **NIH NIH U19** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $3,085,105

## Abstract

Gene editing holds the promise of enhancing the precision and safety of anti-HIV gene therapies based on engineering hematopoietic stem and progenitor cells (HSPC), in order to recreate elements of the Berlin Patient cure. Targeted nuclease technology is already being used to exploit NHEJ-mediated repair of DNA breaks and thereby disrupt the CCR5 gene, which mimics one aspect of his cure. However, extending this treatment to noncancer patients, receiving engineered autologous HSPC, will likely need to include other approaches. To do this, we are exploiting the alternate pathway of DNA break repair based on homology-directed repair (HDR). This can be used to introduce gain-of-function mutations into cellular restriction factors, or to direct the controlled secretion of soluble anti-viral factors, including the broad entry inhibitor eCD4-Ig. Moreover, the site-specific insertion at eCD4-Ig at the CCR5 locus would combine HIV-resistance with systemic protection and thereby provide a combinatorial anti-HIV approach. In the current proposal we aim to continue to improve the safety and efficacy of gene editing in HSPC, and to apply the technology to provide both local and systemic HIV resistance. We will combine our established anti-HIV approaches with a new direction to engineer production of broadly neutralizing antibodies, and thereby provide a novel synthetic immune capability. Individual strategies and combination approaches will be evaluated in appropriate mouse models, to evaluate their impact on HIV infection and the latent reservoir.

## Key facts

- **NIH application ID:** 9891825
- **Project number:** 1U19HL156247-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Paula M Cannon
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,085,105
- **Award type:** 1
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9891825

## Citation

> US National Institutes of Health, RePORTER application 9891825, Novel hematopoietic stem cell engineering and transplantation approaches for HIV cure (1U19HL156247-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9891825. Licensed CC0.

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