Delivery strategies for developing siRNA-based vaginal microbicides

Joseph A. Katakowski, Deborah Palliser

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

RNA interference (RNAi) is a mechanism of posttranscriptional gene silencing, initially described in plants and worms and more recently in mammals. The specificity of siRNAs makes them an attractive modality for therapeutic use, and they are being evaluated in various clinical trials. Studies have shown effective uptake of siRNAs across mucosal surfaces including the lung, rectum, and vagina. Targeting genes in the rectum and vagina could be useful for preventing sexually transmitted diseases such as HIV-1 and HSV-2. However, the main barrier for use of siRNAs in the clinic is delivery. Topically applied siRNAs need to traverse the mucosal layer present in the vagina and resist degradation in the acidic environment. Subsequent uptake of siRNAs by appropriate cells must result in access to the cytosolic compartment where the RNA-induced silencing complex resides. Effective RNAi-mediated gene-specific silencing must be accomplished while minimizing toxic bystander effects. In this chapter we will present the strategies that are being used to achieve these goals.

Original languageEnglish (US)
Title of host publicationMucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies
PublisherSpringer US
Pages345-365
Number of pages21
ISBN (Print)9781461495246, 1461495237, 9781461495239
DOIs
StatePublished - Oct 1 2013

Fingerprint

Vagina
RNA Interference
Anti-Infective Agents
Small Interfering RNA
Rectum
RNA-Induced Silencing Complex
Bystander Effect
Human Herpesvirus 2
Gene Targeting
Poisons
Gene Silencing
Therapeutic Uses
Sexually Transmitted Diseases
HIV-1
Mammals
Clinical Trials
Lung

Keywords

  • Modified siRNA
  • Off-target effects
  • Sexually transmitted disease
  • siRNA
  • siRNA delivery vehicles
  • Vaginal microbicide

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Katakowski, J. A., & Palliser, D. (2013). Delivery strategies for developing siRNA-based vaginal microbicides. In Mucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies (pp. 345-365). Springer US. https://doi.org/10.1007/978-1-4614-9524-6_15

Delivery strategies for developing siRNA-based vaginal microbicides. / Katakowski, Joseph A.; Palliser, Deborah.

Mucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies. Springer US, 2013. p. 345-365.

Research output: Chapter in Book/Report/Conference proceedingChapter

Katakowski, JA & Palliser, D 2013, Delivery strategies for developing siRNA-based vaginal microbicides. in Mucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies. Springer US, pp. 345-365. https://doi.org/10.1007/978-1-4614-9524-6_15
Katakowski JA, Palliser D. Delivery strategies for developing siRNA-based vaginal microbicides. In Mucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies. Springer US. 2013. p. 345-365 https://doi.org/10.1007/978-1-4614-9524-6_15
Katakowski, Joseph A. ; Palliser, Deborah. / Delivery strategies for developing siRNA-based vaginal microbicides. Mucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies. Springer US, 2013. pp. 345-365
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