Polymer nanoparticles encapsulating siRNA for treatment of HSV-2 genital infection
Open accessAbstract
Effective, low-cost, and safe treatments for sexually transmitted viral infections are urgently needed. Here, we show for the first time that intravaginal administration with nanoparticles of poly(lactic-co-glycolic acid) (PLGA) encapsulating short interfering RNA (siRNA) molecules is effective for prevention of genital HSV-2 infections in mice. PLGA nanoparticles (NPs) were designed to interfere with HSV-2 infection by siRNA-mediated knockdown of nectin, a host cell protein. NPs were characterized in vitro to determine the optimal formulation based on siRNA loading, controlled release profile, and mRNA knockdown. Mice inoculated intravaginally with a lethal dose of HSV-2, and treated with PLGA NPs, showed increased survival from ~9 days (in untreated mice) to >28 days (in PLGA NP treated mice) - the longest survival ever observed with siRNA treatment in this mouse model. This work provides proof-of-concept that topical administration of NPs containing siRNA against a pathologically relevant host cell target can knockdown the gene in tissue and improve survival after HSV-2 infection. Furthermore, this system provides a safe delivery platform that employs materials that are already approved by the FDA and can be modified to enhance delivery of other microbicides.
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PLGA nanoparticles had similar knockdown efficiency to lipoplexes, but elicited lower inflammation.
“The authors found that the PLGA nanoparticles had a similar knockdown efficiency to lipoplexes, but elicited lower inflammation (as observed by measuring neutrophil invasion using immunohistochemistry).”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [28]
PLGA nanoparticles containing cationic spermidine have been used for siRNA-based knockdown of the same target, and have shown better protection than lipofectamine lipoplexes.
“Interestingly, PLGA nanoparticles containing cationic spermidine have been used for siRNA-based knockdown of the same target, and have shown better protection than lipofectamine lipoplexes 28 .”
From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [28]
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References 37 · Cited by 113
- Authors
- Steinbach, J. M., Weller, C. E., Booth, C. J., & Saltzman, W. M.
- Affiliations
- Yale University (US)
- Corresponding author
- Saltzman, W. Mark
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 162
- Issue
- 1
- Pages
- 102-110
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC3543782
- OpenAlex
- W2054786837
- Cited by
- 113
- References
- 37
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 6 · 2021: 12 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 14 · 2016: 8 · 2015: 10 · 2014: 16 · 2013: 7 · 2012: 2
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5t32hg003198-10)
- National Human Genome Research Institute (T32-HG 003198)
- National Institute of Allergy and Infectious Diseases (F32AI093056)
- National Institute of Biomedical Imaging and Bioengineering (R01EB000487)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- herpes simplex virus type 2, genital herpes, siRNA delivery, PLGA nanoparticles, vaginal administration, microbicides, sexually transmitted infections, topical drug delivery, controlled release, gene silencing
- MeSH terms
- Nectins, Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Drug Carriers, Female, HeLa Cells, Herpes Genitalis, Humans, Mice, Inbred C57BL, Polyglycolic Acid, Genetic Therapy, Cell Adhesion Molecules, Herpesvirus 2, Human, Lactic Acid, RNA Interference, RNA, Small Interfering, Mice, Nanoparticles, Host-Pathogen Interactions
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