ArticlePLoS pathogens2008
CD4-specific designed ankyrin repeat proteins are novel potent HIV entry inhibitors with unique characteristics.
Article in PLoS pathogens, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Cell-cell transmission enables HIV-1 to evade inhibition by potent CD4bs directed antibodies.PLoS pathogens · 2012Trial
- HIV capsid inhibitors: Mechanisms, resistance, and therapeutic advances.PLoS pathogens · 2026Review
- Bipolar CD4-targeted dual-DARPin-55/57 lipid nanoparticle enables efficient CRISPR/Cas-mediated HIV-1 DNA excision and reactivation blockade in latent CD4 T cell lines.Materials today. Bio · 2026Article
- Genetically Encoded SpyTag Enables Modular AAV Retargeting via SpyCatcher-Fused Ligands for Targeted Gene Delivery.ACS synthetic biology · 2026Article
- Targeted bacteriophage T4 nanoparticles reverse HIV-1 latency in human T cell line models.iScience · 2025Article
- Efficient in vivo generation of CAR T cells using a retargeted fourth-generation lentiviral vector.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- AAV vectors displaying bispecific DARPins enable dual-control targeted gene delivery.Biomaterials · 2023Article
- Multivalent bicyclic peptides are an effective antiviral modality that can potently inhibit SARS-CoV-2.Nature communications · 2023Article
- Dimeric Ankyrin with Inverted Module Promotes Bifunctional Property in Capturing Capsid to Impede HIV-1 Replication.International journal of molecular sciences · 2023Article
- Synonymous Codons and Hydrophobicity Optimization of Post-translational Signal Peptide PelB Increase Phage Display Efficiency of DARPins.ACS synthetic biology · 2022Article
- Review
- Fantastic AAV Gene Therapy Vectors and How to Find Them-Random Diversification, Rational Design and Machine Learning.Pathogens (Basel, Switzerland) · 2022Review
- Regulation of epitope exposure in the gp41 membrane-proximal external region through interactions at the apex of HIV-1 Env.PLoS pathogens · 2022Article
- Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators.Retrovirology · 2021Article
- Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production.Biomolecules · 2021Article
- Protein-Protein Interactions: Insight from Molecular Dynamics Simulations and Nanoparticle Tracking Analysis.Molecules (Basel, Switzerland) · 2021Article
- Empowering patients from within: Emerging nanomedicines for in vivo immune cell reprogramming.Seminars in immunology · 2021Review
- In Situ Programming of CAR T Cells.Annual review of biomedical engineering · 2021Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C) HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins-high physical stability, specificity and low production costs-with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development.
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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.