title: High-density lipoproteins for the systemic delivery of short interfering RNA.
abstract: BACKGROUND
  RNA interference (RNAi) is a powerful mechanism for gene silencing with the potential to greatly impact the development of new therapies for many human diseases. Short interfering RNAs (siRNAs) may be the ideal molecules for therapeutic RNAi. However, therapeutic siRNAs face significant challenges that must be overcome prior to widespread clinical use. Many efforts have been made to overcome the hurdles associated with systemic administration of siRNA; however, current approaches are still limited. As such, there is an urgent need to develop new strategies for siRNA delivery that have the potential to impact a broad spectrum of systemic diseases.
  
  
  METHODS
  This review focuses on the promise of siRNA therapies and highlights current siRNA delivery methods. With an eye toward new strategies, this review first introduces high-density lipoprotein (HDL) and describes its natural biological functions, and then transitions into how HDLs may provide significant opportunities as next-generation siRNA delivery vehicles. Importantly, this review describes how synthetic HDLs leverage the natural ability of HDL to stabilize and deliver siRNAs.
  
  
  CONCLUSIONS
  HDLs are natural nanoparticles that are critical to understanding the systemic delivery of therapeutic nucleic acids, like siRNA. Methods to synthesize biomimetic HDLs are being explored, and data demonstrate that this type of delivery vehicle may be highly beneficial for targeted and efficacious systemic delivery of siRNAs.
authors: Northwestern University, Feinberg School of Medicine, Department of Urology , 303 E. Chicago Avenue, Tarry 16-703, Chicago, IL 60611 , USA +1 312 503 9354 ; +1 312 503 1867 ; cthaxton003@northwestern.edu.
authors: Kaylin Marie
authors: KM
authors: McMahon
authors: Colby Shad
authors: CS
authors: Thaxton
mesh_terms: D000818:Animals; D020868:Gene Silencing; D006801:Humans; D008075:Lipoproteins, HDL / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering