title: Preclinical and clinical development of siRNA-based therapeutics.
abstract: The discovery of RNA interference, first in plants and Caenorhabditis elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment.
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Gulnihal
authors: G
authors: Ozcan
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Bulent
authors: B
authors: Ozpolat
authors: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Robert L
authors: RL
authors: Coleman
authors: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors: Anil K
authors: AK
authors: Sood
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. Electronic address: glopez@mdanderson.org.
authors: Gabriel
authors: G
authors: Lopez-Berestein
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004337:Drug Carriers / Q000737:chemistry; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005260:Female; D018390:Gene Targeting; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D034622:RNA Interference / Q000187:drug effects*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D036104:Receptor, EphA2 / Q000235:genetics*
chemical_list: D004337:Drug Carriers; D034741:RNA, Small Interfering; D036104:Receptor, EphA2
keywords: EphA2; Gene silencing; Nanocarriers; Nanoliposomes; Ovarian cancer; Therapeutic use; siRNA