Title:Cyclodextrins for Non-Viral Gene and siRNA Delivery
Volume: 1
Issue: 1
Author(s): Aoife M. O'Mahony, Martin J. O'Neill, Bruno M.D.C. Godinho, Raphael Darcy, John F. Cryan and Caitriona M. O'Driscoll
Affiliation:
Keywords:
Click chemistry, cyclodextrins, genes, non-viral delivery, pre-clinical, siRNA.
Abstract: Considerable research is focused on the development of non-viral vectors for gene and RNA interference therapies,
with significant advancements in this field over the past number of years. Cationic lipids and polymers have been extensively
investigated for these purposes, but there still remains a need for alternative vectors. Cyclodextrins (CDs) are
cyclic oligosaccharides derived from starch and are well characterised pharmaceutical excipients. They offer many advantages
as potential non-viral vectors for gene and siRNA delivery, in particular the ease with which they can be chemically
modified and their lack of toxicity. In recent years, there has been a surge in the number of publications concerning CDs
in this field. In this paper, we will review the two main approaches to the use of CDs for gene and siRNA delivery. In the
first instance, CDs are used as a scaffold, to which various chemical groups can be grafted, yielding monodisperse functionalised
CDs which can self-assemble in the presence of oligonucleotides. CDs are particularly amenable to chemical
modification and this approach enables specific and precise design of CD vectors for targeting to various cell and tissue
types. In the second approach, CDs can be included as a component of a delivery system, for example, as part of a polymer
backbone, appended to a dendrimeric vector, or in polyrotaxane systems. Here, the inclusion of CDs facilitates postmodification
of the vector through the formation of inclusion complexes with adamantane and, in some instances, reduces
toxicity of the vector. Lastly, we will consider the development of in vivo CD vectors for therapeutic use and other novel
applications including siRNA delivery in neurons and the CNS.
