Extracellular vesicles expressing a single-chain variable fragment of an HIV-1 specific antibody selectively target Env+ tissues
Open accessAbstract
Rationale: Antiretroviral therapy can effectively suppress HIV-1 replication in the peripheral blood to an undetectable level.However, elimination of the latent virus in reservoirs remains a challenge and is a major obstacle in the treatment of HIV-1-infected patients.Exosomes exhibit huge promise as an endogenous drug delivery nanosystem for delivering drugs to solid tissues given their unique properties, including low immunogenicity, innate stability, high delivery efficiency, and most importantly the ability to penetrate solid tissues due to their lipophilic properties.Methods: We engineered and expressed the scFv of a high affinity HIV-1-specific monoclonal antibody, 10E8, on the exosomal surface (10E8 scFv -exos).Subsequently, the 10E8 scFv -exos were loaded with curcumin (Cur), a chemical that kills HIV-1-infected cells, or miR-143, an apoptosis-inducing miRNA.We tested the ability of 10E8 scFv -exos to deliver cargo to Env + target cells and tissues, as well as their ability to suppress HIV-1 infection.Results: 10E8 scFv -exos efficiently targeted CHO cells expressing a trimeric gp140 on their surface (Env + cells) in vitro, as demonstrated by confocal imaging and flow cytometry.10E8 scFv -exos loaded with Cur or miR-143 showed specific killing of Env + cells.In addition, 10E8 scFv -exos loaded with Cur or miR-143 could suppress p24 expression in an HIV-1 latency cell line ACH2 and in PBMCs from an ART-treated HIV-1-infected patient.In an NCG mouse model grafted with tumorigenic Env + CHO cells and which had developed solid tissue tumors, intravenously injected 10E8 scFv -exos targeted the Env-expressing tissues and delivered Cur to induce a strong suppression of the Env + tumor growth with low toxicity.Conclusion: In principle, engineered exosomes can deliver anti-HIV agents to solid tissues by specifically targeting cells expressing viral envelop proteins and inducing cell killing, suggesting that such an approach could be developed for eradicating virus-infected cells in tissue reservoirs.
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Constructs containing the PDGFR transmembrane domain fused to single-chain variable fragments of HIV-1 Env-specific antibodies have been used to target exosomes to HIV-1-infected cells.
“The study by Zou et al. demonstrated that the constructs containing the platelet-derived growth factor receptor (PDGFR) transmembrane domain fused to single-chain variable fragments of human immunodeficiency virus (HIV)-1 Env-specific antibodies have been used to target exosomes to HIV-1-infected cells [24].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [24]
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- Authors
- Zou, X., Yuan, M., Zhang, T., Wei, H., Xu, S., Jiang, N., Zheng, N., & Wu, Z.
- Affiliations
- Nanjing University (CN)
- Model Animal Research Center (CN)
- Nanjing University of Chinese Medicine (CN)
- State Key Laboratory of Analytical Chemistry for Life Science (CN)
- Corresponding author
- Zheng, Nan
- Venue
- Theranostics
- Publisher
- Ivyspring International Publisher
- Published
- 2019
- Volume
- 9
- Issue
- 19
- Pages
- 5657-5671
- ISSN
- 1838-7640 (ISSN-L)
- PMC
- PMC6735399
- OpenAlex
- W2968238138
- Cited by
- 63
- References
- 51
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 13 · 2023: 3 · 2022: 9 · 2021: 10 · 2020: 8
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Theranostics (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Health Commission of the People's Republic of China
- National Key Research and Development Program of China (2016YFC1201000)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- extracellular vesicles, engineered exosomes, scFv, HIV-1 envelope glycoprotein, targeted drug delivery, curcumin, miR-143, HIV-1 latency, viral reservoir, gp140, tumor targeting, antiretroviral therapy
- MeSH terms
- Extracellular Vesicles, RNAi Therapeutics, Animals, Antibodies, Monoclonal, Cricetulus, Curcumin, Feasibility Studies, Female, Humans, HIV Antibodies, HIV-1, HIV Infections, Gene Products, env, CHO Cells, Drug Delivery Systems, Virus Latency, Anti-HIV Agents, MicroRNAs, Mice, Exosomes, Single-Chain Antibodies
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