Description

Lecture by Theresa M. Reineke, Distinguished McKnight University Professor of the Department of Chemistry at The University of Minnesota. 

ABOUT THIS LECTURE

Polymers that assemble with nucleic acids into nanocomplexes (polyplexes) are have been widely examined for many fundamental biological and applied biomedical applications.  However, understanding the binding, encapsulation, and intracellular transport mechanisms and in vivo efficacy of these vehicles remains a significant hurdle in their effective usage and translation. Herein, the synthesis and characterization of several cationic polymer vehicles will be presented that vary in charge density, hydrophilic composition (such as the presence of carbohydrates), architecture, and functionality. We show that the polymer structure impacts the ability of the vehicle to bind and compact nucleic acids into polyplexes. Professor Reinke has performed extensive studies on various polymer structures to understand their in vitro/ex vivo (primary fibroblasts and induced pluripotent stem cells) and in vivo (mouse liver) performance as a function of polymer structure. We show that cellular and in vivo transgene delivery, expression, and toxicity is highly affected by polymer structure. Also, polymer structure played a significant role for in vivo tissue-specific pDNA delivery to the mouse liver. The cellular internalization, trafficking pathways, and intracellular organelle colocalization were also highly affected by vehicle structure. We conclude that the presence and type of carbohydrates displayed on the polymeric vehicle determine in vivo delivery efficacy to the mouse liver and improve ex vivo delivery of CRISPR-Cas9.  

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