Revisiting gene delivery to the brain: Silencing and editing

João Conniot, Sepehr Talebian, Susana Simões, Lino Ferreira, João Conde

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)
29 Downloads (Pure)


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. This journal is

Original languageEnglish
Pages (from-to)1065-1087
Number of pages23
JournalBiomaterials Science
Issue number4
Publication statusPublished - 21 Feb 2021


  • Efficiency
  • Gene therapy
  • Gene transfer
  • Neurodegenerative diseases
  • Vectors


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