Nucleic Acids, Nucleotides, and Nucleosides Commons^™

Development Of Non-Viral Nano-Carriers For Gene Delivery And Covid-19 Vaccines, Zhongyu Li

Dissertations

Gene therapy is one of the most promising medical fields with the potential to effectively advance the treatment of difficult diseases by producing therapeutic proteins or repairing defective gene sequences. However, gene therapy presents severe challenges in delivery including renal clearance, phagocytosis, enzymatic degradation, protein absorption, and cellular internalization barriers, which have been barriers for translation into the clinic. Naked nucleic acids, with their intrinsic negative charge, electrostatically repulse the anionic cell membrane, preventing cellular uptake. Also, they are considered foreign genetic material when introduced into the body and are rapidly cleared by the reticuloendothelial system or degraded by nucleases, …

Synthesis And Characterization Of Antiviral Drug Candidate Molecules Against The Respiratory Syncytial Virus, Ali Abbas Sabi

Dissertations

Abstract

Pyrrole-imidazole polyamides (PAs) are small molecules that typically develop H-bonds to bind to the minor groove of DNA. PAs are of interest because they can be designed to recognize DNA sequences. PAs have numerous biomedical applications in areas like regulation of gene expression and antimicrobial activity. Specifically, polyamide UMSL1011 (a polyamide synthesized in Dr. Bashkin's lab) inhibits replicating vesicular stomatitis virus (VSV) by binding the viral RNA inside the nucleocapsid, as indicated by research at Professor Ming Luo's lab at Georgia State University. However, some reports have revealed that polyamides have a low affinity for “simple” double-stranded RNA. Nevertheless, …

Analysis Of The Intricacies Of Substrate Recognition Of High Mobility Group Proteins And Aminoacyl-Trna Synthetases Using Non-Cognate Substrates, Douglas Van Iverson Ii

Dissertations

The studies presented in section 1 (Chapters I-IV) focus on the design and development of nucleic acid four-way junctions (4WJs) to target a member of the high mobility group (HMG) proteins, the proinflammatory cytokine high mobility group box 1 protein (HMGB1). In the present study, hybrid PNA-DNA 4WJs based on a model DNA 4WJ were constructed to improve the thermal stability of 4WJs while maintaining strong binding affinity toward HMGB1. An electrophoretic mobility shift assay (EMSA) was used to examine the binding affinity of an isolated DNA binding domain of HMGB1, the HMGB1 b-box (HMGB1b), toward a set of PNA-DNA …