Suhba Ranjan Das: Nucleic Acid-Polymer Conjugates and Hybrids for Nanobiotechnology

The ability to conjugate nucleic acids to polymers had yielded rich dividends in new materials with enhanced properties. We have explored facile access to novel biomacromolecular materials and architectures through conjugations of DNA and RNA with polymers.^1-3 Where DNA hybridization in some constructs can be used to drive the assembly and disassembly of soft nanoparticles or to generate non-covalent protein polymer hybrids,^1,2 in other materials, the polymer can confer enhanced properties to the nucleic acid.³ In polymer-escorted passenger siRNAs (PEp-siRNAs), direct conjugation of polymer to the passenger strand of an siRNA duplex confers both enhanced stability to the duplex and cell-permeability to the PEp-siRNA construct that is a robust RNA interference agent.

While the ability to conjugate DNA and RNA to polymers has resulted in novel materials, limitations arise due to the necessity of covalent bond formation between two macromolecules in an appropriate solvent that is compatible with both. To transcend these limitations we have developed an initiator that can be directly incorporated during nucleic acids synthesis and the polymer can be grafted from this initiator either in aqueous solution following synthesis or directly on solid-support.⁴ This approach to DNA-polymer hybrids greatly simplifies purification and expands the range of polymers that can be used with nucleic acids and is leading to new constructs and architectures for bio-sensing and delivery among other applications. This seminar will also cover new results and applications of novel brush polymers functionalized with DNA ‘bristles’. The polymer-brush DNA nanostructure has a high local density of attached DNA that results in properties of the localized DNA that are different from those of an equivalent amount of DNA free in solution. These properties are proving useful in the assembly and retention of fluorescent dyes and provide bright 'nanotags' for imaging applications.