Chemically Programmed Polymers for Targeted DNA and siRNA Transfection

Abstract

Plasmid DNA and siRNA have a large potential for use as therapeutic nucleic acids in medicine. The way to the target cell and its proper compartment is full of obstacles. Polymeric carriers help to overcome the encountered barriers. Cationic polymers can interact with the nucleic acid in a nondamaging way but still require optimization with regard to transfer efficiency and biocompatibility. Aiming at viruslike features, as viruses are the most efficient natural gene carriers, the design of bioresponsive polymers shows promising results regarding DNA and siRNA delivery. By specific chemical modifications dynamic structures are created, programmed to respond towards changing demands on the delivery pathway by cleavage of labile bonds or conformational changes, thus enhancing biocompatible gene delivery.

Three‐Layered Biodegradable Micelles Prepared by Two‐Step Self‐Assembly of PLA‐PEI‐PLA and PLA‐PEG‐PLA Triblock Copolymers as Efficient Gene Delivery System

“…The PEGylation of (hy)PEI is typically accomplished using chemical bonds which are relatively stable in the intracellular environment . The lack of biodegradability of (hy)PEI‐g‐PEG block copolymers prevents timely release of internalized DNA from the complex due to steric interferences of the still associated PEG chains . Furthermore, steric interference of PEG chains reduces PEI's ability to condense DNA into a compact polyplex particle, which coincidently reduces the polyplex micelles' stability in the presence of competing polyanions such as glycosaminoglycans .…”

Regeneration of mammalian cochlear and vestibular hair cells through Hes1/Hes5 modulation with siRNA

“…Higher levels of siRNA molecules can be incorporated into polymer delivery carriers, and enhanced transfection can occur when compared to plasmid DNA for example (Salcher and Wagner, 2010). Silencing RNA technology is rapidly advancing to the clinic (Davis, 2010) and is being applied to the ear (Alvarado et al, 2011, Maeda et al, 2005, Mukherjea et al, 2008).…”

siRNA transfection by dendritic core–shell nanocarriers

“…[275,297] PEI unfortunately displays serious toxic effects and the repeated systemic application as a gene carrier is limited due to the fact that it is nonbiodegradable. [298] Therefore, when designing a new carrier to achieve efficient condensation and cytosolic release with low toxicity, the carrier should be degradable. Various efficient polymers bearing hydrolyzable ester bonds have been designed, whereas the degradable linker is either integrated in the polymer backbone or serves as a cross-linking agent.…”

“…Various efficient polymers bearing hydrolyzable ester bonds have been designed, whereas the degradable linker is either integrated in the polymer backbone or serves as a cross-linking agent. [298] Many research groups generate biodegradable polycations, e.g., by cross-linking nontoxic low molecular weight monomers or oligomers with linkers containing labile bonds. Green et al [117,300] reported, e.g., poly(β-amino ester)s as promising materials because they bind and self-assemble with DNA to form stable nanoparticles that effectively enter cells, escape the endosomal compartments, and degrade via hydrolytic cleavage of backbone ester groups.…”