Current status of non-viral gene therapy for CNS disorders

Expert Opin Drug Deliv. 2016 Oct;13(10):1433-45. doi: 10.1080/17425247.2016.1188802. Epub 2016 Jun 1.


Introduction: Viral and non-viral vectors have been used as methods of delivery in gene therapy for many CNS diseases. Currently, viral vectors such as adeno-associated viruses (AAV), retroviruses, lentiviruses, adenoviruses and herpes simplex viruses (HHV) are being used as successful vectors in gene therapy at clinical trial levels. However, many disadvantages have risen from their usage. Non-viral vectors like cationic polymers, cationic lipids, engineered polymers, nanoparticles, and naked DNA offer a much safer option and can therefore be explored for therapeutic purposes.

Areas covered: This review discusses different types of viral and non-viral vectors for gene therapy and explores clinical trials for CNS diseases that have used these types of vectors for gene delivery. Highlights include non-viral gene delivery and its challenges, possible strategies to improve transfection, regulatory issues concerning vector usage, and future prospects for clinical applications.

Expert opinion: Transfection efficiency of cationic lipids and polymers can be improved through manipulation of molecules used. Efficacy of cationic lipids is dependent on cationic charge, saturation levels, and stability of linkers. Factors determining efficacy of cationic polymers are total charge density, molecular weights, and complexity of molecule. All of the above mentioned parameters must be taken care for efficient gene delivery.

Keywords: Gene delivery; brain delivery; central nervous system; nanobiotechnology; neurological disorders; viral/non-viral vector.

Publication types

  • Review

MeSH terms

  • Cations / chemistry
  • Central Nervous System Diseases / therapy*
  • DNA / administration & dosage
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Humans
  • Lipids / chemistry
  • Polymers / chemistry
  • Transfection


  • Cations
  • Lipids
  • Polymers
  • DNA