The development of siRNA medicine in eye diseases is tremendously useful and encouraging. Successful gene therapy requires excellent siRNA delivery strategies. SiRNA medicines can be coupled with a suitable vector to boost the efficacy of siRNA in treating eye diseases. Numerous other vectors are used for SiRNA delivery investigations besides those described in the article. For example, Cai et al. produced a combination of bioreducible fluorinated peptide dendrimer (BFPD) and siVEGF that greatly improved physiological stability and serum resistance while bypassing all extracellular barriers associated with local siRNA injection. In cell silencing studies, BFPD complexes carrying siVEGF were shown to have high VEGF silencing efficiency (approximately 65%) and robust potential to prevent cell growth. Many siRNA medications, such as bevasiranib, SYL040012, and QPI-1007, were clinically tested. Unfortunately, due to poor clinical results, the phase III clinical study rejected the bevasiranib proposal and other latecomers were not spared. The most obvious limitations affecting the efficiency of siRNA medicines are their poor intrinsic targeting, poor stability, and off-target effects, resulting in much fewer than promised advantages of the medicines, as well as severe adverse effects.The ultimate goal of building an eye medication delivery system for intraocular disease treatments is to produce long-acting pharmacological formulations with precision controlled release rate, biocompatibility, and long-lasting effects on target tissue. Vector form and size may be modified to determine controlled release rate. In preclinical and clinical investigations, intravitreal (IVT) injection and subretinal (SR) injections now deliver most ocular gene therapies, both known to produce inflammation. However, certain siRNA treatments are fragile, requiring frequent injections, raising inflammatory risk. Biodegradable vector research is crucial. Lack of non-viral cell selectivity is a serious limiting factor. Non-viral vectors can be modified to contain targeting features like antibodies or ligands for targeted distribution. CD44, a molecule of cell adhesion, is present in many cells. CD44 expression is 2-6 times more in glaucomatous than healthy cells. HA, as a ligand CD44, allows vectors to target glaucomatous cells. Dillinger et al. created HA-coated nanoparticles that transport siRNA directly to cell surface CD44 receptors against the connective tissue development factor. Cell culture research and perfusion testing in pig, murine, and human organ culture demonstrated that distribution of HA-coated nanoparticles to outflow route cells was more successful than that of PEI-coated nanoparticles.
Retraction notice to ‘Highly antibacterial polypeptide-based amphiphilic copolymers as multifunctional non-viral vectors for enhanced intracellular siRNA delivery and anti-infection’ [ACTBIO 58 (2017) 90–101]
