Molecular therapy : the journal of the American Society of Gene TherapyFeb 4, 2026

Producing an anti-HIV antibody inside mice by inserting genes into primate blood stem cells without using viruses

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 5, 2026

Abstract

CRISPR/Cas12a achieved higher knock-in efficiency with fewer non-specific edits compared to Cas9 in non-human primate hematopoietic stem and progenitor cells.

Non-viral gene editing approaches may support long-term production of antibodies.
Transplantation of edited hematopoietic stem and progenitor cells into MISTRG mice resulted in successful engraftment and B cell differentiation.
Transgene expression was observed for both a reporter transgene and an anti-HIV antibody following immunization.
Detectable antibody titers were present in circulation after immunization with gp120 antigen.
The study suggests potential for sustained biologics production in treating chronic diseases.

Simplified

Gene editing strategies that do not rely on viral vectors are being explored for their potential to support durable biologics production. While clinical trials have shown that adeno-associated virus encoding broadly neutralizing antibodies can protect against HIV, these interventions often yield limited, short-lived responses. The development of non-viral gene editing approaches in hematopoietic stem and progenitor cells holds promise for long-term antibody production. In this study, we evaluated CRISPR/Cas9 and CRISPR/Cas12a for gene knock-in at the immunoglobulin heavy chain locus in non-human primate (NHP) hematopoietic stem and progenitor cells (HSPCs). Delivering the nuclease as a protein alongside a custom DNA template, we optimized editing with Cas12a and demonstrated higher knock-in efficiency and fewer non-specific edits than Cas9. Transplantation of edited NHP HSPCs into MISTRG mice led to engraftment, B cell differentiation, and transgene expression of a reporter transgene or anti-HIV antibody after gp120 antigen immunization with detectable titers in circulation. These findings demonstrate the feasibility of using non-viral knock-in in HSPCs as a potential strategy for sustained biologics production in the treatment of chronic diseases. Future work will assess the efficacy of this approach in a NHP model of HIV infection.

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Competing interests

Declaration of interests J.J.T. is on the advisory board of Bespoke Biotherapeutics and has a patent application held by the Fred Hutchinson Cancer Center related to this work.

PubMed

Producing an anti-HIV antibody inside mice by inserting genes into primate blood stem cells without using viruses

Abstract

Full Text

Funding

Competing interests

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Abstract

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Funding

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Related papers

You found one interesting study. We’ll send the next 7.

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Recent issues from the crispr gene editing brief