Destination Brain the Past Present and Future o

Authors: Chaitanya R Joshi Vinod Labhasetwar Anuja Ghorpade

Publish Date: 2017/02/03

Volume: 12, Issue: 1, Pages: 51-83

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Abstract

Neurological diseases and disorders NDDs present a significant societal burden and currently available drug and biologicalbased therapeutic strategies have proven inadequate to alleviate it Gene therapy is a suitable alternative to treat NDDs compared to conventional systems since it can be tailored to specifically alter select gene expression reverse disease phenotype and restore normal function The scope of gene therapy has broadened over the years with the advent of RNA interference and genome editing technologies Consequently encouraging results from central nervous system CNStargeted gene delivery studies have led to their transition from preclinical to clinical trials As we shift to an exciting gene therapy era a retrospective of available literature on CNSassociated gene delivery is in order This review is timely in this regard since it analyzes key challenges and major findings from the last two decades and evaluates future prospects of brain gene delivery We emphasize major areas consisting of physiological and pharmacological challenges in gene therapy functionbased selection of a ideal cellular targets available therapy modalities and diversity of viral vectors and nanoparticles as vehicle systems Further we present plausible answers to key questions such as strategies to circumvent low bloodbrain barrier permeability and most suitable CNS cell types for targeting We compare and contrast pros and cons of the tested viral vectors in the context of delivery systems used in past and current clinical trials Gene vector design challenges are also evaluated in the context of cellspecific promoters Key challenges and findings reported for recent gene therapy clinical trials assessing viral vectors and nanoparticles are discussed from the perspective of bench to bedside gene therapy translation We conclude this review by tying together gene delivery challenges available vehicle systems and comprehensive analyses of neuropathogenesis to outline future prospects of CNStargeted gene therapies

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