Nucleic acids are anionic biopolymers, which have promise as novel therapeutics for a number of acquired and inherited diseases. Polynucleotides of many different architectures have exceptional affinity and specificity for their intracellular targets. Plasmids (pDNA), oligonucleotides, small interfering RNA (siRNA), messenger RNA (mRNA), and CRISPR-Cas9 gene editing systems are common therapeutic payloads being examined clinically in this field. Delivery systems are needed to compact these sensitive payloads into nanostructures, protect nucleic acids from enzymatic damage during transport, promote cellular entry, 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 gene therapy and gene editing purposes. In addition, we aim to develop new experimental methods to gain a fundamental understanding of their interactions and pathways taken within living systems in a spatial and temporal manner. These systems are being carefully investigated by our group to build fundamental structure-property relationships that describe how polymers complex with nucleic acids and interact with their biological environment, in addition to understanding toxicity mechanisms (or lack thereof). In this area, our lab is highly collaborative with researchers in several science and engineering departments, the medical school, and corporate partners.

Yaming TOC

Featured Projects: Nucleic Acid Delivery

Print This Account describes the collective efforts and contributions by the Reineke Group to develop carbohydrate-based cationic polymers (glycopolymers) for nonviral gene delivery applications.

Reference: C. Van Bruggen, J. K. Hexum, Z. Tan, R. J. Dalal, T. M. Reineke "Nonviral Gene Delivery with Cationic Glycopolymers", Acc. Chem. Res. 2019, 52, 1347–1358. [ACS Editors' Choice]
Boyle TOC - Final This publication describes the use of small molecule additives, including chloroquine and dexamethasone, to destabilize nuclear membranes (a transfection barrier) in addition to the effect of plasmid size on the transfection efficiency of primary human cells.

Reference: W. Boyle, K. Twaroski, E. Woska, J. Tolar, T. M. Reineke "Molecular additives significantly enhance glycopolymer-mediated transfection of large plasmids and functional CRISPR-Cas9 transcription activation ex vivo in primary human fibroblasts and induced pluripotent stem cells", Bioconjugate Chem. 2019, 30, 418–431.