Vectors and strategies for nonviral cancer gene therapy

SUMMARY

Introduction: This review presents recent developments in the use of nonviral vectors and transfer technologies in cancer gene therapy. Tremendous progress has been made in developing cancer gene therapy in ways that could be applicable to treatments. Numerous efforts are focused on methods of attacking known and novel targets more efficiently and specifically. In parallel to progress in nonviral vector design and delivery technologies, important achievements have been accomplished for suicide, gene replacement, gene suppression and immunostimulatory therapies. New nonviral cancer gene therapies have been developed based on emerging RNAi (si/shRNA-, miRNA) or ODN.

Areas covered: This review provides an overview of recent gene therapeutic strategies in which nonviral vectors have been used experimentally and in clinical trials. Furthermore, we present current developments in nonviral vector systems in association with important chemical and physical gene delivery technologies and their potential for the future.

Expert opinion: Nonviral gene therapy has maintained its position as an approach for treating cancer. This is reflected by the fact that more than 17% of all gene therapy trials employ nonviral approaches. Thus, nonviral vectors have emerged as a clinical alternative to viral vectors for the appropriate expression and delivery of therapeutic genes.

KEYWORDS:

• Cancer
• Gene therapy
• gene transfer
• nonviral vectors

Article highlights

• Cancer still represents the major field of pre-clinical and clinical activities in gene therapy

• Nonviral vectors have evolved to useful tools for cancer gene therapy and meanwhile represent a valuable, clinically applicable alternative to viral vectors.

• Nonviral vectors have been significantly improved regarding their efficiency in gene transfer, transgene expression and safety parameters. Significant size reduction, removal of unnecessary sequences and optimized expression cassettes are key achievements for these improved features.

• The recent developments of novel nonviral vectors enabled targeted genomic integration associated with prolonged transgene expression.

• Nonviral vectors are also successfully used for gene suppression strategies based on optimized oligodexynucleotide and on si/shRNA and miRNA technologies.

• Improvements of nonviral vectors is paralleled by tremendous advancements in physical and chemical transfer technologies to aid efficient gene delivery and which already entered clinical.

This box summarizes key points contained in the article.

Acknowledgements

We thank Nicholas C. Fiorenza and Russ Hodge for critical reading of the manuscript.

Declaration of interest

Supported by grants from Deutsche Krebshilfe (DKH), Germany and by H&J Hector Foundation, Mannheim, Germany. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.