Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

Abstract

Non-viral vectors have emerged as a promising alternative to viral gene delivery systems due to their safer profile. Among non-viral vectors, recently, niosomes have shown favorable properties for gene delivery, including low toxicity, high stability, and easy production. The three main components of niosome formulations include a cationic lipid that is responsible for the electrostatic interactions with the negatively charged genetic material, a non-ionic surfactant that enhances the long-term stability of the niosome, and a helper component that can be added to improve its physicochemical properties and biological performance. This review is aimed at providing recent information about niosome-based non-viral vectors for gene delivery purposes. Specially, we will discuss the composition, preparation methods, physicochemical properties, and biological evaluation of niosomes and corresponding nioplexes that result from the addition of the genetic material onto their cationic surface. Next, we will focus on the in situ application of such niosomes to deliver the genetic material into immune-privileged tissues such as the brain cortex and the retina. Finally, as future perspectives, non-invasive administration routes and different targeting strategies will be discussed.

Scaffold-Mediated Gene Delivery for Osteochondral Repair

“…Gene transfer via nonviral vectors (transfection) is the incorporation of the DNA plasmid (pDNA) either alone or complexed with cationic or ionizable lipids (lipoplexes), cationic polymers (polyplexes), or a combination of both (lipopolyplexes) [ 35 ] into the target cell population [ 36 ] ( Table 1 ). More recent approaches also include the use of niosomes (nioplexes) [ 37 ], dendrimers (dendriplexes) [ 38 ], and gold or carbon nanostructures [ 39 ]. Nonviral vectors are generally considered safe carriers compared with viral constructs as they do not carry the risk of insertional mutagenesis (nonviral vectors are kept under episomal forms) and have a low immunogenicity (nonviral vectors have no intrinsic viral coding sequences) [ 40 ].…”

Efficient Gene Delivery Based on Guanidyl‐Nucleic Acid Molecular Interactions

“…[ 10 ] Adopting a non‐intravenous administration approach could ensure that gene complexes effectively escape nuclease degradation and phagocytosis by the reticuloendothelial system. [ 11 ] However, non‐intravenous administration of gene complexes still encounters other physiological barriers. First, dilution in local tissue by interstitial fluid leads to rapid elimination of gene complexes at the administration site.…”

Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy

“…Ocular gene therapy has the potential to cure or relieve symptoms of inherited or acquired diseases by replacing a defective gene with a normal gene [1,2]. This chance to cure by correcting the cause of the disorder means an important advantage compared with conventional drugs that, in most cases, only can suppress symptoms [3,4]. Furthermore, gene therapy provides long-term benefits compared with small drugs for ocular therapeutics whose effects usually last few hours.…”

“…Several approaches have been tested to drive genes to the cornea [1,4,7,12]. Non-viral vector therapy relies on physical methods (mechanical, electrical, or surgical procedures) that deliver naked DNA, or chemical methods (high salt solutions and polycation carriers) that enhance entry of nucleic acid into cells [1,10,[12][13][14].…”

“…Non-viral vector therapy relies on physical methods (mechanical, electrical, or surgical procedures) that deliver naked DNA, or chemical methods (high salt solutions and polycation carriers) that enhance entry of nucleic acid into cells [1,10,[12][13][14]. Naked DNA is quite unstable, and thus a variety of non-viral nanocarriers based on inorganic particles, liposomes, and cationic lipids and polymers (e.g., polylysine, polyarginine, chitosan) have been proposed [4,15]. Typically, non-viral vectors may establish electrostatic interactions with both the nucleic acid (forming complexes) and the cell surface facilitating attachment and subsequent endocytosis [16].…”