ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Reprogramming of the heavy-chain CDR3 regions of a human antibody repertoire.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- CD98hc-targeted antibody shuttles for central nervous system delivery with broad cross-species reactivity.Nature biomedical engineering · 2026Article
- In vivo production of an anti-HIV antibody in mice by non-viral gene knockin in primate hematopoietic stem and progenitor cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- B lymphocyte protein factories produced by hematopoietic stem cell gene editing.Science (New York, N.Y.) · 2026Article
- B Lymphocyte Protein Factories produced by Hematopoietic Stem Cell Gene Editing.bioRxiv : the preprint server for biology · 2026Article
- Enhanced B cell electroporation efficiency via inhibition of DNA-induced apoptosis and pyroptosis with pan-caspase inhibitor.Molecular therapy. Methods & clinical development · 2025Article
- Engineering B cells to treat and study human disease.Nature biotechnology · 2025Review
- Mouse B cells engineered to express an anti-HPV antibody elicit anti-tumor T cell responses.Frontiers in immunology · 2025Article
- In vivo affinity maturation of the CD4 domains of an HIV-1-entry inhibitor.Nature biomedical engineering · 2024Article
- Reprogramming human B cells with custom heavy-chain antibodies.Nature biomedical engineering · 2024Article
- Single-hit genome editing optimized for maturation in B cells redirects their specificity toward tumor antigens.Scientific reports · 2024Article
- In vivo affinity maturation of mouse B cells reprogrammed to express human antibodies.Nature biomedical engineering · 2024Article
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- Heavy-chain CDR3-engineered B cells facilitate in vivo evaluation of HIV-1 vaccine candidates.Immunity · 2023Article
- Adenoviral vectors infect B lymphocytes in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- In vitro affinity maturation of broader and more-potent variants of the HIV-1-neutralizing antibody CAP256-VRC26.25.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
B cells have been engineered ex vivo to express an HIV-1 broadly neutralizing antibody (bNAb). B cell reprograming may be scientifically and therapeutically useful, but current approaches limit B cell repertoire diversity and disrupt the organization of the heavy-chain locus. A more diverse and physiologic B cell repertoire targeting a key HIV-1 epitope could facilitate evaluation of vaccines designed to elicit bNAbs, help identify more potent and bioavailable bNAb variants, or directly enhance viral control in vivo. Here we address the challenges of generating such a repertoire by replacing the heavy-chain CDR3 (HCDR3) regions of primary human B cells. To do so, we identified and utilized an uncharacterized Cas12a ortholog that recognizes PAM motifs present in human JH genes. We also optimized the design of 200 nucleotide homology-directed repair templates (HDRT) by minimizing the required 3'-5' deletion of the HDRT-complementary strand. Using these techniques, we edited primary human B cells to express a hemagglutinin epitope tag and the HCDR3 regions of the bNAbs PG9 and PG16. Those edited with bNAb HCDR3 efficiently bound trimeric HIV-1 antigens, implying they could affinity mature in vivo in response to the same antigens. This approach generates diverse B cell repertoires recognizing a key HIV-1 neutralizing epitope.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.