ArticleGene therapy2014
A novel gene therapy strategy using secreted multifunctional anti-HIV proteins to confer protection to gene-modified and unmodified target cells.
Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
8 citing papers in PubMed, 11 citations in OpenAlex.
- Protein- and Peptide-Based Virus Inactivators: Inactivating Viruses Before Their Entry Into Cells.Frontiers in microbiology · 2020Review
- Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41.Viruses · 2019Review
- HIV Entry and Its Inhibition by Bifunctional Antiviral Proteins.Molecular therapy. Nucleic acids · 2018Review
- Genetic Strategies for HIV Treatment and Prevention.Molecular therapy. Nucleic acids · 2018Review
- Control of HIV Infection In Vivo Using Gene Therapy with a Secreted Entry Inhibitor.Molecular therapy. Nucleic acids · 2017Article
- Further Characterization of the Bifunctional HIV Entry Inhibitor sCD4-FIMolecular therapy. Nucleic acids · 2017Article
- Lentiviral expression system for the purification of secreted proteins from human cell cultures.BMC biotechnology · 2016Article
- Bone Marrow Gene Therapy for HIV/AIDS.Viruses · 2015Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Current human immunodeficiency virus type I (HIV) gene therapy strategies focus on rendering HIV target cells non-permissive to viral replication. However, gene-modified cells fail to accumulate in patients and the virus continues to replicate in the unmodified target cell population. We have designed lentiviral vectors encoding secreted anti-HIV proteins to protect both gene-modified and unmodified cells from infection. Soluble CD4 (sCD4), a secreted single chain variable fragment (sscFv(17b)) and a secreted fusion inhibitor (sFI(T45)) were used to target receptor binding, co-receptor binding and membrane fusion, respectively. Additionally, we designed bi- and tri-functional fusion proteins to exploit the multistep nature of HIV entry. Of the seven antiviral proteins tested, sCD4, sCD4-scFv(17b), sCD4-FI(T45) and sCD4-scFv(17b)-FI(T45) efficiently inhibited HIV entry. The neutralization potency of the bi-functional fusion proteins sCD4-scFv(17b) and sCD4-FI(T45) was superior to that of sCD4 and the Food and Drug Administration-approved fusion inhibitor T-20. In co-culture experiments, sCD4, sCD4-scFv(17b) and sCD4-FI(T45) secreted from gene-modified producer cells conferred substantial protection to unmodified peripheral blood mononuclear cells. In conclusion, continuous delivery of secreted anti-HIV proteins via gene therapy may be a promising strategy to overcome the limitations of the current treatment.
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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.