Non-viral nucleic acid delivery methods

ABSTRACT

Introduction: Delivery of nucleic acid-based molecules in human cells is a highly studied approach for the treatment of several disorders including monogenic diseases and cancers. Non-viral vectors for DNA and RNA transfer, although in general less efficient than virus-based systems, are particularly well adapted mostly due to the absence of biosafety concerns. Non-viral methods could be classified in two main groups: physical and vector-assisted delivery systems. Both groups comprise several different methods, none of them universally applicable. The choice of the optimal method depends on the predefined objectives and the features of targeted micro-environment.

Areas covered: In this review, the authors discuss non-viral techniques and present recent therapeutic achievements in ex vivo and in vivo nucleic acid delivery by most commonly used techniques while emphasizing the role of ‘biological particles’, namely peptide transduction domains, virus like particles, gesicles and exosomes.

Expert opinion: The number of available non-viral transfection techniques used for human therapy increased rapidly, followed by still moderate success in efficacy. The prospects are to be found in design of multifunctional hybrid systems that reflect the viral efficiency. In this respect, biological particles are very promising.

KEYWORDS:

• Nucleic acid delivery
• physical transfection
• particle mediated transfection
• peptide transduction domains
• virus derived particles
• exosomes

Article highlights box

• For consistent therapeutic administration, non-viral nucleic acid vectors need to ensure high transfection efficiency, precise cell targeting and scalability of delivery to humans.

• Current trends and future perspectives on non-viral vectors development are moving rapidly toward design of multi-functional and multi-domain structures. Although still far behind viral techniques considering transfection efficacy, the steady advancement is evident in both physical and particle based nucleic acid trafficking.

• Concerning gene and cell therapy with either DNA or RNA, physical methods currently represent a large majority of non-viral transfection strategies undergoing clinical trials focused mostly on cancer and infectious diseases treatment.

• Combination of viral efficiency and chemical particle tractability opens a way for design of highly effective and safe biomolecular vehicles for gene therapy. In that sense development of chemically functionalized transfection peptides of (non)viral origin and extracellular vesicles represents a rapidly growing field of research.

Declaration of interest

D Guay is an employee of Feldan Therapeutics. 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.

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Funding

This manuscript has not been funded.