ArticleEBioMedicine2018
Synthetic DNA delivery by electroporation promotes robust in vivo sulfation of broadly neutralizing anti-HIV immunoadhesin eCD4-Ig.
Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- DNA Vaccines in the Post-mRNA Era: Engineering, Applications, and Emerging Innovations.International journal of molecular sciences · 2025Review
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- Delivery of DNA-Based Therapeutics for Treatment of Chronic Diseases.Pharmaceutics · 2024Review
- Adeno-associated virus-vectored delivery of HIV biologics: the promise of a "single-shot" functional cure for HIV infection.Journal of virus eradication · 2023Article
- Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer.Nature communications · 2022Article
- Techniques for Developing and Assessing Immune Responses Induced by Synthetic DNA Vaccines for Emerging Infectious Diseases.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Review: Development of SARS-CoV-2 immuno-enhanced COVID-19 vaccines with nano-platform.Nano research · 2022Review
- A DNA-Launched Nanoparticle Vaccine Elicits CD8Cancer immunology research · 2020Article
- Article
- DNA vaccines: prime time is now.Current opinion in immunology · 2020Review
- In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure-Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection fromVaccines · 2020Article
- Harnessing Recent Advances in Synthetic DNA and Electroporation Technologies for Rapid Vaccine Development Against COVID-19 and Other Emerging Infectious Diseases.Frontiers in medical technology · 2020Review
- Development of Novel DNA-Encoded PCSK9 Monoclonal Antibodies as Lipid-Lowering Therapeutics.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundDespite vigorous and ongoing efforts, active immunizations have yet to induce broadly neutralizing antibodies (bNAbs) against HIV-1. An alternative approach is to achieve prophylaxis with long-term expression of potent biologic HIV-1 inhibitors with Adeno-associated Virus (AAV), which could however be limited by hosts' humoral and cellular responses. An approach that facilitates in vivo production of these complex molecules independent of viral-vectored delivery will be a major advantage.
methodsWe used synthetic DNA and electroporation (DNA/EP) to deliver an anti-HIV-1 immunoadhesin eCD4-Ig in vivo. In addition, we engineered a TPST2 enzyme variant (IgE-TPST2), characterized its intracellular trafficking patterns and determined its ability to post-translationally sulfate eCD4-Ig in vivo.
findingsWith a single round of DNA injection, a peak expression level of 80-100μg/mL was observed in mice 14 days post injection (d.p.i). The engineered IgE-TPST2 enzyme trafficked efficiently to the Trans-Golgi Network (TGN). Co-administrating low dose of plasmid IgE-TPST2 with plasmid eCD4-Ig enhanced the potency of eCD4-Ig by three-fold in the ex vivo neutralization assay against the global panel of HIV-1 pseudoviruses.
interpretationThis work provides a proof-of-concept for delivering anti-HIV-1 immunoadhesins by advanced nucleic acid technology and modulating protein functions in vivo with targeted enzyme-mediated post-translational modifications.
fundingThis work is supported by NIH IPCAVD Grant U19 Al109646-04, Martin Delaney Collaboration for HIV Cure Research and W.W. Smith Charitable Trust.
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