ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Engineering Protein-Secreting Plasma Cells by Homology-Directed Repair in Primary Human B Cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 141 citations in OpenAlex.
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- B cell αv integrin regulates tissue specialization and clonal expansion of lung germinal center and memory B cells after viral infection.Science advances · 2026Article
- Engineering B cells to express fully customizable antibodies with enhanced Fc functions.Nature communications · 2026Article
- Modeling human B cell development with pluripotent stem cells.bioRxiv : the preprint server for biology · 2026Article
- Engineered hematopoietic stem cells give rise to therapeutic antibody secreting B cells.Research square · 2026Article
- Humanized mice enableMolecular therapy. Advances · 2026Article
- B Lymphocyte Protein Factories produced by Hematopoietic Stem Cell Gene Editing.bioRxiv : the preprint server for biology · 2026Article
- A precision gene-engineered B cell medicine producing sustained levels of active factor IX for hemophilia B therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration.Nature biotechnology · 2025Article
- Innovative gene engineering and drug delivery systems for dendritic cells in cancer immunotherapy.Journal of biomedical science · 2025Review
- Production Technologies for Recombinant Antibodies: Insights into Eukaryotic, Prokaryotic, and Transgenic Expression Systems.Biochemical genetics · 2025Review
- 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 Express Fully Customizable Antibodies with Enhanced Fc Functions.Research square · 2025Article
- B cell αv integrin regulates tissue specialization and clonal expansion of lung germinal center and memory B cells after viral infection.bioRxiv : the preprint server for biology · 2025Article
- Engineering B cells to treat and study human disease.Nature biotechnology · 2025Review
- Article
- Targeting human plasma cells using regulated BCMA CAR T cells eliminates circulating antibodies in humanized mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Microbead-based synthetic niches for in vitro expansion and differentiation of human naïve B-cells.Bioengineering & translational medicine · 2025Article
- Advances in development of antiviral strategies against respiratory syncytial virus.Acta pharmaceutica Sinica. B · 2025Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The ability to engineer primary human B cells to differentiate into long-lived plasma cells and secrete a de novo protein may allow the creation of novel plasma cell therapies for protein deficiency diseases and other clinical applications. We initially developed methods for efficient genome editing of primary B cells isolated from peripheral blood. By delivering CRISPR/CRISPR-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes under conditions of rapid B cell expansion, we achieved site-specific gene disruption at multiple loci in primary human B cells (with editing rates of up to 94%). We used this method to alter ex vivo plasma cell differentiation by disrupting developmental regulatory genes. Next, we co-delivered RNPs with either a single-stranded DNA oligonucleotide or adeno-associated viruses containing homologous repair templates. Using either delivery method, we achieved targeted sequence integration at high efficiency (up to 40%) via homology-directed repair. This method enabled us to engineer plasma cells to secrete factor IX (FIX) or B cell activating factor (BAFF) at high levels. Finally, we show that introduction of BAFF into plasma cells promotes their engraftment into immunodeficient mice. Our results highlight the utility of genome editing in studying human B cell biology and demonstrate a novel strategy for modifying human plasma cells to secrete therapeutic proteins.
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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.