bm-2014-001229_0007The wealth of information being obtained from genomic, proteomic, and glycomic research is allowing researchers to unravel the intricate genetic and epigenetic mechanisms associated with human health and disease. Ubiquitous tools such as miRNA (microRNA), siRNA (small interfering RNA), oligodeoxynucleotide (ODN) transcription factor decoys, plasmid DNA, aptamers, genetic vaccines, and many other polynucleotide forms are transforming the methods of regulating gene expression and epigenetic mechanisms for understanding biological processes, disease pathways, and are undergoing extensive research and development as novel therapeutics.

Nucleic acids have exceptional affinity and specificity for their intracellular targets; yet, many complex factors dictate the accuracy, reproducibility, and relevance of utilizing polynucleotides as novel therapeutics. Delivery systems are needed to compact nucleic acids into nanostructures, termed polyplexes, that can enter cells, protect nucleic acids from enzymatic damage, and provide the possibility of targeting the delivery to specific tissue types and sites within the cell.

We strive to creatively design innovative polymeric vehicles for delivering gene regulatory nucleic acids and develop new experimental methods to gain a fundamental understanding of their interactions and pathways taken within living systems in a spatial and temporal manner. We have developed several novel carbohydrate-containing polymers that have shown outstanding affinity to form polyplexes and facilitate intracellular nucleic acid delivery efficiency with low toxicity. These systems are being carefully investigated to build fundamental structure-property relationships describing how polymers complex with nucleic acids and interact with its biological environment. Ultimately, we are concerned with the design, synthesis, and biological characterization, as well as with the examination of the mechanism of delivery of polymers.

Featured Projects

Screen-Shot-2015-03-24-at-2.15.23-PMPolyelectrolyte complexes (PECs) play an important role in gene delivery. The goal of this project is to study the complexation of DNA with cationic block copolymer micelles by quantifying the formation, structure, and properties of resulting micelleplexes. This study aims to further the physical understanding of how DNA interacts with cationic polymers and apply the fundamental understanding in designing polymeric gene delivery vehicles of desired physical properties. [In preparation]
mz-2012-00660t_0005 Cationic polymers have been explored heavily in recent years as a promising modality for gene delivery. Many exciting advances have been made with polymeric delivery vehicles; yet more work is needed to further advance these systems toward the clinic. The anionic nature of polynucleotides enables the electrostatic complexation with cationic polymers, giving rise to nanoscale complexes termed polyplexes. Ideally, polymeric vehicles would efficiently bind nucleic acids to form colloidally stable polyplexes that have the ability to circulate in the blood, facilitate endocytosis into the targeted tissue, and ultimately release their cargo once inside the cell. In addition, the polyplexes must exhibit low cellular and immunotoxicity and avoid rapid clearance by the reticuloendothelial system. To further understand the role of charge type and block length of polymer gene delivery vehicles, a family of copolymers was generated comprising polyMAG and polymethacrylates of various block lengths bearing secondary, tertiary, and quaternary amine functionalities. [Read more]