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

Abstract

Gene therapy is the gene transfer into host cells for treatment of acquired and genetic disorders. For this purpose, there are a wide variety of gene delivery methods with special properties including viral and non-viral vectors. The non-viral methods use physical forces or chemical compounds (natural or synthetic) to transfer DNA into a cell. The efficiency of the non-viral gene therapy depends on conquering four different intra-and extra-cellular barriers such as cellular uptake, endosomal escape, nuclear entry, and gene expression. Among various gene carriers, some viral vectors such as Adenovirus, Lentivirus, Vaccinia as well as gene gun and lipofection achieved to clinical trials. In this mini-review, we briefly describe different approaches for gene delivery and their applications in various phases of clinical trials.

Current State of the Art in DNA Vaccine Delivery and Molecular Adjuvants: Bcl-xL Anti-Apoptotic Protein as a Molecular Adjuvant

“…In the method, usually the stratum corneum and the viable epidermis are breached by microneedles, after which DNA can be delivered into the dermis. There are several different microneedle methods for DNA delivery; solid microneedles can be coated with DNA prior to skin penetration, uncoated microneedles can be used to damage the epidermis prior to application of a transdermal patch containing the DNA of interest, solid microneedles constructed with biopolymers can be coated with DNA such that the needles dissolve upon contact with the fluid in the dermis to release DNA into the skin and hollow microneedles can deliver DNA into the dermis through the needles [28][29][30]. Quantitative introduction of multiple components into the same cell is an advantage of this technique, while technical skills are required to prevent cell damage [31].…”

“…Momentum allows penetration of these particles to a few millimeters of the tissue and then cellular DNA release. Gas pressure, particle size and dose frequency are critical factors in determining the degree of tissue damage and penetration effectiveness of the application [18,28]. This method has various advantages such as safety, high efficiency against parenteral injection, total amount of DNA required for delivery is low, no receptor is required, size of DNA is not a problem and production of DNA-coated metal particles is easy to generate.…”

“…This technique is a widely tested method for intramuscular, intradermal and intratumoral genetic immunization. The use of gene gun for gene therapy against various cancers in clinical trials has also been demonstrated [18,[28][29][30].…”

“…This device is commonly used to deliver medications through the skin for intradermal, subcutaneous and intramuscular applications. Usually, CO 2 pressure is used to force medications (e.g., vaccine) loaded in the device through a tiny orifice, which creates a high-pressure stream capable of penetrating the skin in the absence of a needle [28][29][30]. Biojectors have been used to deliver different kinds of vaccines such as DNA vaccine, in preclinical studies and human clinical trials to elicit significantly higher antibody responses and cell-mediated immunity (CMI) to the conventional (needle and syringe) vaccine delivery systems [29].…”

“…Because biojector-based delivery systems can increase the uptake of DNA in tissues of the skin and muscle, efficacy of the DNA vaccine is considerably increased. In a phase 1 trial for HIV vaccine, the success demonstrated with biojector used to enhance the efficiency of DNA transfection coupled with the fact that biojectors do not use needles that will most likely lead to the increased use of biojectors for DNA delivery in the clinic [28][29][30].…”