Nonviral Gene Therapy for Cancer: A Review.

Chiaki Hidai,Hisataka Kitano

doi:10.3390/diseases6030057

Abstract

Although the development of effective viral vectors put gene therapy on the road to commercialization, nonviral vectors show promise for practical use because of their relative safety and lower cost. A significant barrier to the use of nonviral vectors, however, is that they have not yet proven effective. This apparent lack of interest can be attributed to the problem of the low gene transfer efficiency associated with nonviral vectors. The efficiency of gene transfer via nonviral vectors has been reported to be 1/10th to 1/1000th that of viral vectors. Despite the fact that new gene transfer methods and nonviral vectors have been developed, no significant improvements in gene transfer efficiency have been achieved. Nevertheless, some notable progress has been made. In this review, we discuss studies that report good results using nonviral vectors in vivo in animal models, with a particular focus on studies aimed at in vivo gene therapy to treat cancer, as this disease has attracted the interest of researchers developing nonviral vectors. We describe the conditions in which nonviral vectors work more efficiently for gene therapy and discuss how the goals might differ for nonviral versus viral vector development and use.

Highlights

Cancer therapy around the world consists mainly of surgery, chemotherapy, radiotherapy, and multimodality therapy
We introduce case studies where in vivo treatment using nonviral vectors resulted in a survival benefit in animal models of cancer, for which a high gene transfer efficiency is required
Compared the adenovirus vector and polyethylenimine (PEI), another representative nonviral vector, and found that PEI was 10 to 1000 times less effective than the adenovirus vector. These findings suggest that the use of nonviral vectors for gene therapy is unrealistic

Summary

Introduction

Cancer therapy around the world consists mainly of surgery, chemotherapy, radiotherapy, and multimodality therapy. Gene therapy using viral vectors has recently been proven to be an efficient approach, as exemplified by excellent results obtained using viral-mediated cytotherapy to treat diseases caused by genetic deficiencies, a clear area of interest for gene therapy-based approaches [1,2]. Among such successes are lentiviral hematopoietic stem cell cytotherapy, used to treat metachromatic leukodystrophy, and viral vector-based approaches, used to treat Wiskott–Aldrich syndrome. It seems possible that nonviral approaches might never be practical as gene therapy targeting genetic deficiencies, but this does not mean that they are without potential value. We refer readers to other reviews for information on new technologies and novel nonviral vectors currently in development [5,9,10,11]

Gene Transfer Efficiency of Nonviral Vectors

Efficiency of Gene Therapy with Nonviral Vectors

Gene Therapy for Diseases Other Than Cancer

Gene Therapy for Cancer

Findings

Conclusions