Polymer–Nucleic Acid Interactions

Abstract

Gene therapy is an important therapeutic strategy in the treatment of a wide range of genetic disorders. Polymers forming stable complexes with nucleic acids (NAs) are non-viral gene carriers. The self-assembly of polymers and nucleic acids is typically a complex process that involves many types of interaction at different scales. Electrostatic interaction, hydrophobic interaction, and hydrogen bonds are three important and prevalent interactions in the polymer/nucleic acid system. Electrostatic interactions and hydrogen bonds are the main driving forces for the condensation of nucleic acids, while hydrophobic interactions play a significant role in the cellular uptake and endosomal escape of polymer-nucleic acid complexes. To design high-efficiency polymer candidates for the DNA and siRNA delivery, it is necessary to have a detailed understanding of the interactions between them in solution. In this chapter, we survey the roles of the three important interactions between polymers and nucleic acids during the formation of polyplexes and summarize recent understandings of the linear polyelectrolyte-NA interactions and dendrimer-NA interactions. We also review recent progress optimizing the gene delivery system by tuning these interactions.

Design of Oligonucleotide Carriers: Importance of Polyamine Chain Length

“…Increasing the DNA length and N/P ratio results in disappearance of the negatively charged complex. Nucleic acids can interact with amines by the means of ionic interactions through phosphate groups or by hydrogen bonds through nucleobases [40,41] and references in this review. The latter mechanism suggests that the negatively charged free phosphate groups compensates the positive charge of the free amine units.…”

Structure Validation of G‐Rich RNAs in Noncoding Regions of the Human Genome

“…Their fundamental building blocks are planar tetrads composed of four guanine nucleobases (G‐tetrad) that engage in Hoogsteen‐type base pairing (Scheme A) . Typically, two to four of these tetrads are stacked on top of each other to form the structural motif, though larger assemblies have been reported as well (Scheme B) . G‐quadruplex folding requires monovalent cations, such as K + or Na + , because the positive charge stabilizes the partially negatively charged O6 atoms of the guanine bases .…”

<p>Nano-Graphene Oxide-supported APTES-Spermine, as Gene Delivery System, for Transfection of pEGFP-p53 into Breast Cancer Cell Lines</p>

“…20 Indeed, it is known that a strong electrostatic interaction exists between the phosphate groups of DNA and the amino groups of spermine, as well as hydrophobic and hydrogen bonds. 21 Nanoparticles stability and nucleic acid protection are important parameters for efficient nucleic acid delivery. 22 Release profiles of nanoparticles made with GOAS-pEGFP-p53 incubated in PBS showed that these structures were able to release DNA constantly over 30 days.…”