Nonviral Gene Therapy for Cancer: A Review

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.

Non-Viral Vector Mediated Gene Delivery: the Outsider to Watch Out For in Gene Therapy

“…Viral vectors are generally chosen for their ability to infect both dividing and quiescent cells, required to restore functionality of a defective gene in all cells of the targeted tissue. This main advantage is counterbalanced by immunogenicity and manufacturing bottlenecks [2]. To decrease immunogenicity, modified viral vectors with minimal viral genome are preferred.…”

Metallo-Liposomes of Ruthenium Used as Promising Vectors of Genetic Material

“…Nanocarriers with diverse structures and characteristics have been developed in the last decade to enhance the pharmacological action of drugs and to mitigate the side effects produced by the use of naked pharmaceuticals [3][4][5][6]. Nowadays, many studies about gene therapy are being carried out as a promising option to treat numerous acquired diseases such as cancer, AIDS or genetic disorders [7][8][9][10][11][12]. Biological defense mechanisms of the human body against the presence of foreign substances obligate the researchers to synthesize biocompatible and biodegradable nanosystems, also known as vectors, able to protect the genetic material.…”

Encapsulation, Visualization and Expression of Genes with Biomimetically Mineralized Zeolitic Imidazolate Framework‐8 (ZIF‐8)

“…Other important cationic polymers like poly l ‐lysine, one of the most often used polymers for the complexing and delivery of DNA, have been known to be cytotoxic and possess low capacities for maintaining DNA integrity and endosomal escape . Due to such conflicting reports, up to the year 2018 only 0.24% were reported to examine the use of nonviral delivery systems through gene therapy . The limitations arise from the significant challenges of overcoming three barriers in gene delivery: maintaining the chemical and physical integrity of DNA; successful entry through the cell membrane; and endosomal escape prior to nuclear uptake for expression of the gene through transcription and translation .…”

“…[9] Due to such conflicting reports, up to the year 2018 only 0.24% were reported to examine the use of nonviral delivery systems through gene therapy. [14] The limitations arise from the significant challenges of overcoming three barriers in gene delivery: maintaining the chemical and physical integrity of DNA; successful entry through the cell membrane; and endosomal escape prior to nuclear uptake for expression of the gene through transcription and translation. [15] Therefore, the development of improved synthetic systems that allow the vector to address the above limitations is essential.…”