Shorter, Susan, Gollings, Alexander, Gorringe-Pattrick, Monique, Coakley, Emma, Dyer, Paul D.R. and Richardson, Simon ORCID: 0000-0002-7927-0649 (2016) The potential of toxin-based drug delivery systems for enhanced nucleic acid therapeutic delivery. Expert Opinion on Drug Delivery, 14 (5). pp. 685-696. ISSN 1742-5247 (Print), 1744-7593 (Online) (doi:https://doi.org/10.1080/17425247.2016.1227781)

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Abstract

Introduction: The potential of gene replacement therapy has been underscored by the market authorisation of alipogene tiparvovec (Glybera) and GSK2696273 (Strimvelis) in the EU and recombinant adenovirus-p53 (Gendicine) in China. Common to these systems is the use of attenuated viruses for “drug” delivery. Whilst viral delivery systems are being developed for siRNA, their application to antisense delivery remains problematic. Non-viral delivery remains experimental, with some notable successes. However, stability and the “PEG dilemma”, balancing toxicity and limited (often liver-tropic) PK-PD, with the membrane destabilising activity, necessary for nucleocytosolic access and transfection remain a problem.

Areas Covered: Here we review the use of attenuated protein toxins as a delivery vehicle for nucleic acids, their relationship to the PEG-dilemma, and their biological properties with specific reference to their intracellular trafficking.

Expert opinion: The possibility of using attenuated toxins as antisense and siRNA delivery systems has been demonstrated in vitro. Systems based upon attenuated anthrax toxin have been shown to have high activity (equivalent to nucleofection) and low toxicity whilst not requiring cationic “helpers” or condensing agents, divorcing these systems from the problems associated with the PEG dilemma. It remains to be seen whether these systems can operate safely, efficiently and reproducibly, in vivo or in the clinic.

Item Type:	Article
Uncontrolled Keywords:	Antisense; Drug Delivery; Endocytosis; Gene Therapy; siRNA; Toxin
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Education, Health & Human Sciences > School of Human Sciences (HUM)
Last Modified:	09 Oct 2021 04:45
URI:	http://gala.gre.ac.uk/id/eprint/15700

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