Oral non-viral gene delivery for applications in DNA vaccination and gene therapy

Abstract

Non-viral gene delivery via the oral route is a promising strategy for improving outcomes of DNA vaccination and gene therapy applications. Unlike traditional parenteral administration routes, the oral route is a non-invasive approach that lends itself to high patient compliance and ease of dosing. Moreover, oral administration allows for both local and systemic production of therapeutic genes or, in the case of DNA vaccination, mucosal and systemic immunity. However, the oral route presents distinct challenges and barriers to achieving successful gene delivery. Oral non-viral gene delivery systems must be able to survive the harsh and variable environments (e.g. acidic pH, degrading enzymes, mucus layer) encountered during transit through the gastrointestinal tract, while still allowing for efficient transgene production at sites of interest. These barriers present unique design challenges for researchers in material selection and in improving the transfection efficiency of orally delivered genes. This review provides an overview of advancements in the design of oral non-viral gene delivery systems, and highlights recent and important developments towards improving orally delivered genes for applications in gene therapy and DNA vaccination.

Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals

“…In the case of anionic MPs, their surfaces have been functionalized with thiol functional groups to exhibit mucoadhesive properties by forming disulfide bonds with thiol groups existing in mucins [102,103,104,105,106,107]. Several studies have confirmed that such chemically-modified MPs show a significantly longer residence time in the target, acting as potential candidates for the sustained oral delivery of specific drugs, such as insulin and losartan [96,108].…”

Yeasts in nanotechnology-enabled oral vaccine and gene delivery

“…In the biomedical genetics community, the greater emphasis on eliminating the causative factors underlying a disease rather than treating symptoms has led to the rapid development of approaches to gene therapy and gene delivery. Oral gene delivery has the potential to treat diseases specific to the gastrointestinal tract (GIT) such as ulcerative colitis and cancer and may also have broader therapeutic effects for diseases such as Type 2 diabetes [ 4 ]…”

Effect of Extracellular Matrix Coating on Cancer Cell Membrane-Encapsulated Polyethyleneimine/DNA Complexes for Efficient and Targeted DNA Delivery In Vitro

“…Even if their ability to deliver genes is maintained, additional modifications are needed to achieve tissue specificity. 9,10 Among various cationic polymers, PEI has been widely used as a benchmark polymeric vector. 11,12 PEI condenses DNA to nanosized complexes (polyplexes) to facilitate endocytosis.…”

“…Although these materials are effective delivery agents in in vitro experiments, they are often ineffective when used in vivo. Even if their ability to deliver genes is maintained, additional modifications are needed to achieve tissue specificity. , …”