Issue 4, 2021

Revisiting gene delivery to the brain: silencing and editing

Abstract

Neurodegenerative disorders, ischemic brain diseases, and brain tumors are debilitating diseases that severely impact a person's life and could possibly lead to their demise if left untreated. Many of these diseases do not respond to small molecule therapeutics and have no effective long-term therapy. Gene therapy offers the promise of treatment or even a cure for both genetic and acquired brain diseases, mediated by either silencing or editing disease-specific genes. Indeed, in the last 5 years, significant progress has been made in the delivery of non-coding RNAs as well as gene-editing formulations to the brain. Unfortunately, the delivery is a major limiting factor for the success of gene therapies. Both viral and non-viral vectors have been used to deliver genetic information into a target cell, but they have limitations. Viral vectors provide excellent transduction efficiency but are associated with toxic effects and have limited packaging capacity; however, non-viral vectors are less toxic and show a high packaging capacity at the price of low transfection efficiency. Herein, we review the progress made in the field of brain gene therapy, particularly in the design of non-toxic and trackable non-viral vectors, capable of controlled release of genes in response to internal/external triggers, and in the delivery of formulations for gene editing. The application of these systems in the context of various brain diseases in pre-clinical and clinical tests will be discussed. Such promising approaches could potentially pave the way for clinical realization of brain gene therapies.

Graphical abstract: Revisiting gene delivery to the brain: silencing and editing

Associated articles

Article information

Article type
Review Article
Submitted
31 Jūl. 2020
Accepted
23 Nov. 2020
First published
24 Nov. 2020

Biomater. Sci., 2021,9, 1065-1087

Revisiting gene delivery to the brain: silencing and editing

J. Conniot, S. Talebian, S. Simões, L. Ferreira and J. Conde, Biomater. Sci., 2021, 9, 1065 DOI: 10.1039/D0BM01278E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements