ArticleNature biomedical engineering2024
In vivo affinity maturation of the CD4 domains of an HIV-1-entry inhibitor.
Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- Harnessing the central dogma: Enzyme-driven gene diversification strategies for in cellulo continuous directed evolution.Fundamental research · 2026Review
- Article
- Transgenesis in Drug Discovery: Enhancing Target Identification and Validation.Molecular biotechnology · 2026Review
- B Lymphocyte Protein Factories produced by Hematopoietic Stem Cell Gene Editing.bioRxiv : the preprint server for biology · 2026Article
- Engineering B cells to treat and study human disease.Nature biotechnology · 2025Review
- CRISPR/Cas9 for achieving postintervention HIV control.Current opinion in HIV and AIDS · 2025Review
- Optimizing kinase and PARP inhibitor combinations through machine learning and in silico approaches for targeted brain cancer therapy.Molecular diversity · 2025Article
- Harnessing the FOXO-SIRT1 axis: insights into cellular stress, metabolism, and aging.Biogerontology · 2025Review
- The interplay of p16INK4a and non-coding RNAs: bridging cellular senescence, aging, and cancer.Biogerontology · 2025Review
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17 authors.
Funding
Abstract
Human proteins repurposed as biologics for clinical use have been engineered through in vitro techniques that improve the affinity of the biologics for their ligands. However, the techniques do not select against properties, such as protease sensitivity or self-reactivity, that impair the biologics' clinical efficacy. Here we show that the B-cell receptors of primary murine B cells can be engineered to affinity mature in vivo the human CD4 domains of the HIV-1-entry inhibitor CD4 immunoadhesin (CD4-Ig). Specifically, we introduced genes encoding the CD4 domains 1 and 2 (D1D2) of a half-life-enhanced form of CD4-Ig (CD4-Ig-v0) into the heavy-chain loci of murine B cells and adoptively transferred these cells into wild-type mice. After immunization, the B cells proliferated, class switched, affinity matured and produced D1D2-presenting antibodies. Somatic hypermutations in the D1D2-encoding region of the engrafted cells improved the binding affinity of CD4-Ig-v0 for the HIV-1 envelope glycoprotein and the inhibitor's ability to neutralize a panel of HIV-1 isolates without impairing its pharmacokinetic properties. In vivo affinity maturation of non-antibody protein biologics may guide the development of more effective therapeutics.
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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.