Systemic tumor-specific gene delivery

Abstract

The objective of a systemically administered cancer gene therapy is to achieve gene expression that is isolated to the tumor tissue. Unfortunately, viral systems have strong affinity for the liver, and delivery from non-viral cationic systems often results in high expression in the lungs. Non-specific delivery to these organs must be overcome if tumors are to be aggressively treated with genes such as IL-12 which activates a tumor immune response, and TNF-alpha which can induce tumor cell apoptosis. Techniques which have led to specific expression in tumor tissue include receptor targeting through ligand conjugation, utilization of tumor specific promoters and viral mutation in order to take advantage of proteins overexpressed in tumor cells. This review analyzes these techniques applied to liposomal, PEI, dendrimer, stem cell and viral gene delivery systems in order to determine the techniques that are most effective in achieving tumor specific gene expression after systemic administration.

Nanoemulsion-templated polylelectrolyte multifunctional nanocapsules for DNA entrapment and bioimaging

“…The main techniques of genetic delivery involve the use of genetically modified viruses, non-viral gene transfers and formation of DNA complexes with inorganic salts, polycations, surfactants, or lipids [1,[4][5][6]. Up to now, viral vectors have been the most frequently applied, but they have several potential disadvantages, such as immunogenicity, insertional mutations, and potential pathogenicity [2]. In contrast, non-viral delivery systems are characterized by several benefits including low cost, non-infectivity, absence of immunogenicity, and the possibility of repeated clinical administration [3].…”

“…The main challenges for the delivery of genetic material lie in the poor cellular penetration and targeting delivery without degradation [1][2][3]. For example, a negatively charged DNA biomacromolecule cannot be taken up by cell membranes without the aid of transporters or vectors owing to its unfavourable surface charge and hydrodynamic volume.…”

Cationic Polymer Nanoparticles for Drug and Gene Delivery

“…Viral and non-viral vectors are used for gene delivery. 170,171 Retroviruses and adeno-associated viruses are the most popular viral vectors for gene delivery. These vectors have a natural mechanism to deliver their genetic materials into the host cells.…”

Glycosylation-mediated targeting of carriers

“…Recently, various nucleic acids have been developed for medication including pDNA, antisense DNA, small interfering RNA (siRNA), and microRNA [11][12][13][14][15]. The receptor-mediated targeting by glycosylation has been used for therapy with nucleic acids.…”