Chapter - Targeted Delivery of Short Interfering RNAs - Strategies for In Vivo Application

Targeted Delivery of Short Interfering RNAs - Strategies for In Vivo Application

Author(s): Ahmad F. Hussain, Ulrich Wullner, Inga Neef, Mehmet K. Tur and Stefan Barth

Pp: 228-253 (26)

* (Excluding Mailing and Handling)

Abstract

During the last decade, an increased amount of oligonucleotides have been developed as promising therapeutic agents for treatment of diseases. siRNA/shRNA is one promising example of therapeutic oligonucleotides which can inhibit target gene expression by degrading mRNA in a highly sequence-specific manner. Although, siRNA shows potential therapeutic properties, the specific delivery remains a major barrier for clinical development of siRNA-based drugs. In this chatper, we provide an overview of current progress in the field of siRNA/shRNA delivery and discuss recent patents and technical advances in the development of efficient small RNA delivery vehicles including strategies to enhance their pharmacokinetic properties, to promote their cellular uptake, and to foster corresponding clinical trials.

Keywords: Acute kidney injury, age-related macular edema, alpha v beta 3 integrin, aptamer, aptamer siRNA chimera, C-C chemokine receptor type 5, cell-specific ligands, chronic myeloid leukemia, clinical trials, familial adenomatous polyposis, heregulin receptor, human immunodeficiency virus, hypercholersterolemia, nonarteric ischemic optic neuropathy, non-targeted delivery, ocular hypertension glaucoma, pachyonychia congenital, prostate specific membrane antigen, respiratory syncytial virus, RNA interference, shRNA, siRNA, stable acid lipid particles, transthyretin-mediated amyloidosis, viral siRNA delivery.