Title:Translational siRNA Therapeutics Using Liposomal Carriers: Prospects & Challenges
Volume: 12
Issue: 4
Author(s): Dhiraj Bhavsar, Krishnakumar Subramanian, Swaminathan Sethuraman and Uma Maheswari Krishnan
Affiliation:
Keywords:
Cationic liposomes, Designer lipids, Hybrid liposomes, siRNA.
Abstract: Gene silencing has emerged as a promising strategy for molecular therapy of various malignant, viral, hereditary
and inflammatory disorders. However, its translation from lab to clinic is yet to gain momentum due to the numerous
problems that plague its development. A multi–functional siRNA delivery system with desired properties such as enhanced
immune compatibility, target specificity, high cell uptake and excellent silencing efficiency is required to understand
the challenges involved in the selection and modification of small interfering RNA (siRNA), factors influencing the
complexation process and the response of the biological system to the formulation. Liposomes have been used as delivery
systems due to its versatility in handling different types of drugs, tunable size, charge and surface functionalities that improve
its effectiveness in vivo. This review highlights the challenges involved in gene silencing and describes the progression
of liposomal systems used in gene silencing. The rationale in introducing chemical modifications in siRNA, synthesizing
designer cationic lipids and evolution of hybrid liposomal systems has been elaborated, emphasizing their merits
and short–comings. Finally, a description of the current state of clinical trials involving liposomal formulations has been
included to provide an unbiased perspective of the future of liposomal systems and gene silencing tools as therapeutic
tools.
