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Combined Lentiviral and RNAi Technologies for the Delivery and Permanent Silencing of the hsp25 Gene

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Molecular Chaperones

Part of the book series: Methods in Molecular Biology ((MIMB,volume 787))

Abstract

Elevated heat shock protein 27 (Hsp27) expression has been found in a number of tumors, including breast, prostate, gastric, uterine, ovarian, head and neck, and tumor arising from the nervous system and urinary system, and determined to be a predictor of poor clinical outcome. Although the mechanism of action of Hsp27 has been well documented, there are currently no available inhibitors of Hsp27 in clinical trials. RNA interference (RNAi) has the potential to offer more specificity and flexibility than traditional drugs to silence gene expression. Not surprisingly, RNAi has become a major focus for biotechnology and pharmaceutical companies, which are now in the early stages of developing RNAi therapeutics, mostly based on short interfering RNA (siRNAs), to target viral infection, cancer, hypercholesterolemia, cardiovascular disease, macular degeneration, and neurodegenerative diseases. However, the critical issues associated with RNAi as a therapeutic are delivery, specificity, and stability of the RNAi reagents. To date, the delivery is currently considered the biggest hurdle, as the introduction of siRNAs systemically into body fluids can result in their degradation, off-target effects, and immune detection. In this chapter, we discuss a method of combined lentiviral and RNAi-based technology for the delivery and permanent silencing of the hsp25 gene.

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Acknowledgments

This work was supported in part by Research Advancement Awards from Scott & White Memorial Hospital and Clinic (G.M.N. and P.K.), Institutional support from Scott & White Memorial Hospital and Clinic, Texas A&M Health Science Center College of Medicine, the Central Texas Veterans Health Administration, an Endowment from the Cain Foundation, and the US National Institutes of Health grant RO1CA91889 (A.A.).

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Authors and Affiliations

  1. Division of Investigative Pathology, College of Medicine, Scott & White Memorial Hospital and Clinic, Temple, TX, USA

    Punit Kaur, Ganachari M. Nagaraja & Alexzander Asea

  2. Texas A&M Health Science Center, Temple, TX, USA

    Punit Kaur & Ganachari M. Nagaraja

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  1. Punit Kaur
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  2. Ganachari M. Nagaraja
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  3. Alexzander Asea
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Correspondence to Alexzander Asea .

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Editors and Affiliations

  1. Beth Israel Deaconess Medical Center, Department of Radiation Oncology, Harvard Medical School, Brookline Ave 330, Boston, 02215, Massachusetts, USA

    Stuart K. Calderwood

  2. National Cancer Institute, Urologic Oncology Branch, National Institutes of Health, Rockville Pike 9000, Bethesda, 20814, Maryland, USA

    Thomas L. Prince

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Kaur, P., Nagaraja, G.M., Asea, A. (2011). Combined Lentiviral and RNAi Technologies for the Delivery and Permanent Silencing of the hsp25 Gene. In: Calderwood, S., Prince, T. (eds) Molecular Chaperones. Methods in Molecular Biology, vol 787. Humana Press. https://doi.org/10.1007/978-1-61779-295-3_10

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  • DOI: https://doi.org/10.1007/978-1-61779-295-3_10

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