title: Combined lentiviral and RNAi technologies for the delivery and permanent silencing of the hsp25 gene.
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.
authors: Division of Investigative Pathology, College of Medicine, Scott & White Memorial Hospital and Clinic, Temple, TX, USA.
authors: Punit
authors: P
authors: Kaur
authors: Ganachari M
authors: GM
authors: Nagaraja
authors: Alexzander
authors: A
authors: Asea
mesh_terms: D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems; D005821:Genetic Techniques; D005822:Genetic Vectors; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006360:Heat-Shock Proteins; D016086:Lentivirus / Q000378:metabolism*; D018832:Molecular Chaperones; D009369:Neoplasms / Q000401:mortality; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use*
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering