Nonviral Approach for Targeted Nucleic Acid Delivery

Abstract

Despite their relatively lower efficiency, nonviral approaches are emerging as safer alternatives in gene therapy to viral vectors. Delivery of nucleic acids to the target site is an important factor for effective gene expression (plasmid DNA) or knockdown (siRNA) with minimal side effects. Direct deposition at the target site by physical methods, including ultrasound, electroporation and gene gun, is one approach for local delivery. For less accessible sites, the development of carriers that can home into the target tissue is required. Cationic peptides, lipoplexes, polyplexes and nanoplexes have been used as carriers for delivery of nucleic acids. Targeting ligands, such as cell targeting peptides, have also been applied to decorate delivery vehicles in order to enhance their efficacy. This review focuses on delivery strategies and recent progress in non-viral carriers and their modifications to improve their performance in targeting and transfection.

Different strategies of gene delivery for treatment of cancer and other disorders

“…[18,19] Microinjection: In microinjection, cell membrane or nuclear membrane is penetrated by simple mechanical force using a needle of 0.5 µm-5 µm diameter. [5,20] This gene delivery system is mainly used to inject DNA constructs in vivo.…”

“…[21] Jet injection: In jet injection method, mechanical compression is utilized to move fluid containing DNA without using any needle for injection of particles. [18] Balistic DNA injection or gene gun: The particle bombardment or gene gun uses heavy metal microparticles (e.g., gold or tungsten, 1 µm-5 µm in diameter) to penetrate the target cells. [20][21][22] This method has two major advantages such as safety, and high efficiency against parenteral injection.…”

“…Major disadvantage is that it induces greater immune responses than microinjection. [18,20] Figure 1A shows the use of gene gun for gene therapy against cancer in clinical trials.…”

“…[22,23] This approach has been effectively applied in humans in order to enhance gene transfer and tested in several clinical trials such as leukemia, brain carcinomas, prostate cancer, colorectal cancer, malignant melanoma, Alzheimer, Parkinson, and depression. [8,18] Major disadvantage is that it often results in a high incidence of cell death. [5,11] Sonoporation or ultrasound: Ultrasound, as a non-invasive and site-specific approach, can deliver DNA into the cells by making nanomeric pores in cell membrane and subsequently destroy tumor cells after systemic delivery.…”

Dielectrophoretically-assisted electroporation using light-activated virtual microelectrodes for multiple DNA transfection

“…7 An alternative gene transfection approach, physical methods, presents many advantages to overcome these drawbacks, including relative safety, low toxicity, simple preparation, and the ability to transfect large DNA. 8 Among the physical methods, electroporation is the most well-known and can be applied to various cell types. 9 In electroporation, a high voltage is applied onto target cells to cause a transiently permeable state in the cellular membrane, allowing exogenous molecules (e.g.…”