Biology Reference
In-Depth Information
Chapter 9
RNAi Therapeutic Delivery by Exosomes
Samira Lakhal , Samir El Andaloussi , Aisling J. O'Loughlin ,
Jinghuan Li , and Matthew M. J. Wood
Abstract
Since the discovery of short interfering RNAs (siRNAs), their potential
as a therapeutic platform has been widely recognized. However, clinical translation
has been stalled by inefficient delivery in vivo. While some success has been
achieved with cationic lipids and lipid-like materials for therapeutic RNAi delivery
to liver, delivery across the blood-brain barrier (BBB) to the central nervous system
for the treatment of neurological disorders such as Parkinson's, Alzheimer's, and
Huntington's disease remains a challenge. To address the problem of inefficient
delivery across the BBB, our laboratory exploited one of nature's mechanisms for
intercellular communication, named exosomes. They are a class of membrane ves-
icles derived from the endolysosomal compartment implicated in cell-cell commu-
nication by shuttling various proteins, lipids, and RNAs between cells. We have
developed a method to target exosomes with brain-specific peptides and subse-
quently load them with siRNA for targeted delivery to brain. This chapter aims at
providing an insight into membrane vesicle-mediated RNA delivery and how these
vectors can be utilized for RNAi therapy.
9.1
Introduction
RNAi has revolutionized molecular biology by allowing silencing of virtually any
gene. A key mediator of RNAi is the 19-21 nucleotide duplex RNA (siRNA) that
associate with the RNA-inducing silencing complex (RISC) in the cytoplasm and
direct the highly specific cleavage of complementary mRNAs [
1,
2
] . Since the ini-
tial discovery in 1998 by Fire and Mello [
3
], siRNA have been exploited both as a
Samira Lakhal and Samir El Andaloussi have equally contributed.
S. Lakhal • S. E. Andaloussi • A.J. O'Loughlin • J. Li • M. M. J. Wood (
*
)
Department of Physiology, Anatomy and Genetics , University of Oxford , Oxford , UK
e-mail: matthew.wood@dpag.ox.ac.uk
Search WWH ::
Custom Search