Current status of non-viral gene therapy for CNS disorders

ABSTRACT

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
• central nervous system
• viral/non-viral vector
• brain delivery
• neurological disorders
• nanobiotechnology

Article highlights

• Possible strategies to improve non-viral vector system

• Non-viral vectors must have superior nuclear import ability, extended gene expression and persistence in nucleus.

• Must have ability to proficiently interact with serum constituents without losing the therapeutic cargo.

• Should have longer circulating time in the body and better bio-distribution with better escaping ability from reticuloendothelial system or macrophage system.

• Should have controlled intracellular trafficking ability (i.e. Endosomes release and escaping power from degradation by endonucleases).

• Should have better cell targeting ability, ability to transcription and no cytotoxicity.

This box summarizes key points contained in the article.

Acknowledgment

Author’s acknowledge Institute of NeuroImmune Pharmacology (INIP) and Center for Personalized NanoMedicine (CPNM) for the research support and facility.

Declaration of interest

This work was supported by the National Institute on Drug Abuse [RO1DA027049, RO1DA037838, RO1DA040537, RO1DA042706A]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

1. The merger between lysosomes and endosomes begin the process of degradation and thus this escape from lysosomes increases the chances for a successful DNA transfection