Nucleic Acids, Nucleotides, and Nucleosides Commons^™

Charge Modulation Of Peptide/Nucleic Acid Complexes: An Anionic Additive Enhances Gene Silencing And Crispr/Cas9 Editing By Promoting Intracellular Nucleic Acid Release, Abdulelah Alhazza, Sorour Khayyatnejad Shoushtari, Hasan Uludag, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Introduction: Small interfering RNA (siRNA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated Protein 9 (Cas9) complexes are effective approaches to temporarily downregulate protein expression via post-transcription RNA interference or permanently altering protein expression via editing genomic DNA, respectively. However, the efficient delivery of these mediators to targeted cells has been challenging, largely due to their anionic and hydrophilic nature, which hinders their interaction with the cell membrane and cellular internalization. Cell-penetrating peptides (CPPs) exhibit dual characteristics as a carrier for nucleic acid delivery, where positively charged components bind to the negatively charged nucleic acid, and the hydrophobic components …

Computational Insights Into Nucleosome Dynamics In Epigenetics Using Molecular Dynamics Simulations, Rutika Patel

Dissertations, Theses, and Capstone Projects

Nucleosome core particles (NCP) are the building blocks that form a highly organized and compact chromatin structure. Nucleosomes package DNA in the nucleus of eukaryotic cells. The NCP consists of about 147 base pairs of DNA wrapped around the histone octamer, with 1.65 superhelical turns in a left-handed manner. The histone octamer is composed of two copies of H3, H4, H2A, and H2B. Together with histone H1 and linker DNA, they further assemble into a higher-order chromatin structure. The nucleosome complex is stabilized by electrostatic interactions between positively charged histone residues and the negatively charged DNA backbone. To effectively access …

Dna Strand Breaks By Small Molecules: From Genomic Hazard To Therapeutic Strategy, Clerin John

Honors Scholar Theses

DNA strand breaks are among the most critical forms of genomic damage, arising from endogenous metabolic activity, environmental stress, radiation, and diverse chemical agents. Single-strand breaks and double-strand breaks contribute to genome instability, mutagenesis, carcinogenesis, and neurodegenerative disorders. Cells rely on DNA repair pathways to detect these breaks and initiate repair. In this review, we conducted a comprehensive literature review to systematically compile and examine the mechanisms underlying small-molecule-induced DNA strand breaks. This review highlights the underlying mechanisms by which these molecules interact with DNA and trigger damage. We further discussed the current methods used for detection and quantification of …

Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković

Administration and Staff Articles and Research

Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles …

Defining Rna Oligonucleotides That Reverse Deleterious Phase Transitions Of Rna-Binding Proteins With Prion-Like Domains., Lin Guo, Jacob Mann, Jocelyn Mauna, Katie Copley, Hejia Wang, Jack Rubien, Cristian Bergmann, Jenny Carey, Jessica Merjane, Marilyn Ngo, Jiazhen Xu, Hana Odeh, Jiabei Lin, Bo Lim Lee, Laura Ganser, Emma Robinson, Kevin Kim, Anastasia Murthy, Tapas Paul, Bede Portz, Amanda Gleixner, Zamia Diaz, Ashleigh Smirnov, George Padilla, Ellen Lavorando, Carolann Espy, Yulei Shang, Eric Huang, Alessandra Chesi, Nicolas Fawzi, Sua Myong, Christopher Donnelly, James Shorter

Department of Biochemistry and Molecular Biology Faculty Papers

RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs that prevent FUS fibrillization by promoting liquid phases and distinct short RNAs that prevent and reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. We define a short RNA that dissolves cytoplasmic FUS aggregates, restores nuclear FUS, and mitigates FUS toxicity in optogenetic models and ALS …

Micrornas In Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, And Treatment Monitoring, Seyyed Mohammad Yaghoubi, Erfan Zare, Sina Jafari Dargahlou, Maryam Jafari, Mahdiye Azimi, Maedeh Khoshnazar, Solmaz Shirjang, Behzad Mansoori

Student Papers, Posters & Projects

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are …

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk, Yasir A. Alshehry, Matthew S. Halquist Phd, Sandro R.P. Da Rocha Phd

Graduate Research Posters

Background

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance …

Photo And Spatial Control Of Rna Structures And Functions: Exploring Positional Effects And Photo-Responsiveness Of Azobenzene Modified Nucleotides, Jinxi Du

Electronic Theses & Dissertations (2024 - present)

RNA molecules perform many important biological functions by forming complex three-dimensional structures stabilized by base pairing, tertiary interactions, and metal ion coordination. Because RNA function depends strongly on its structure, methods that allow reversible control of RNA conformation and activity are important for understanding RNA behavior and for potential therapeutic applications. However, achieving reversible and site-specific control of RNA structure, especially at the single-nucleotide level, remains challenging. In this dissertation, I developed and applied azobenzene-modified nucleotides as a chemical tool to enable optical and spatial control of RNA structure and function.

The first part of this dissertation focuses on establishing …

Effects Of Dietary Perfluorobutane Sulfonate (Pfbs) On Adipose Tissue, Hannah Olofintuyi, Eric Gato

Honors College Theses

Per- and polyfluoroalkyl substances (PFAS) are chemical substances used in a variety of industrial applications and consumer products. Perfluorobutane sulfonate (PFBS) is often used as a replacement for the more harmful (Perfluoroalkyl sulfonate) PFAS chemicals that have been around longer. It is believed that PFBS does not remain in the body as long as other PFAS compounds; however, there is a rising concern that it has the potential to cause damage to human health. This study focused on understanding how dietary PFBS exposure affects metabolism-related processes in adipose tissues in rats. To accomplish study objectives, Sprague Dawley rats were exposed …