Therapeutic potential of adenoviral vectors for delivery of expressed RNAi activators
Authors: Mowa, Mohube Betty; Crowther, Carol; Arbuthnot, Patrick
Source: Expert Opinion on Drug Delivery, Volume 7, Number 12, December 2010 , pp. 1373-1385(13)
Publisher: Informa Healthcare
Abstract:Importance of the field: Harnessing RNA interference (RNAi) to silence pathology-causing genes has shown promise as a mode of therapy. The sustained gene inhibition that may be achieved with expressed sequences is potentially useful for treatment of chronic viral infections, but efficient and safe delivery of these sequences remains a challenge. It is generally recognized that there is no ideal vector for all therapeutic RNAi applications, but recombinant adenovirus vectors are well suited to hepatic delivery of expressed RNAi activators.
Areas covered in this review: Adenoviruses are hepatotropic after systemic administration, and this is useful for delivering expressed RNAi activators that silence pathology-causing genes in the liver. However, drawbacks of adenoviruses are toxicity and diminished efficacy, which result from induction of innate and adaptive immune responses. In this review, the advantages and hurdles facing therapeutic application of adenoviral vectors for liver delivery of RNAi effectors are covered.
What the reader will gain: Insights into adenovirus vectorology and the methods that have been used to make these vectors safer for advancing clinical application of RNAi-based therapy.
Take home message: Adenoviruses are very powerful hepatotropic vectors. To make adenoviruses more effective for clinical use, polymer conjugation and deletion of viral vector sequences have been used successfully. However, further modifications to attenuate immunostimulation as well as improvements in large-scale production are necessary before the therapeutic potential of adenovirus-mediated delivery of RNAi activators is realized.
Document Type: Research Article
Affiliations: University of the Witwatersrand, School of Pathology, Antiviral Gene Therapy Research Unit, Health Sciences Faculty, Private Bag 3, WITS 2050, South Africa +27 0 11 717 2365; +27 0 11 717 2395;, Email: Patrick.Arbuthnot@wits.ac.za
Publication date: December 1, 2010