At the O’Reilly Lab, our vision is to transform the lives of patients and families affected by rare and ultra-rare diseases by developing innovative genetic medicines. Driven by compassion and scientific excellence, we aim to advance oligonucleotide therapeutics, such as ASOs, siRNAs, and CRISPR-based technologies, to address urgent unmet medical needs. By combining cutting-edge research with a patient-centered approach, we strive to expand treatment options, deepen our understanding of genetic medicine, and make a meaningful impact on the rare disease community.
We leverage three main classes of oligonucleotide therapeutics:
Our team utilizes expertise in oligonucleotide synthesis, biochemical assays, and in vivo pharmacology to translate discoveries into clinical applications. We address challenges like targeted delivery and cellular uptake and improve our understanding of oligonucleotide interactions with biological systems, including binding to RNA or DNA, modulation of gene expression, intracellular trafficking, and engagement with proteins and immune pathways to optimize efficacy and safety. Through collaboration with academic and clinical partners, we accelerate research and advance therapeutic solutions for rare diseases.
Altering the natural structure of RNA and DNA has been essential for improving the stability and efficacy of oligonucleotide therapeutics. Innovations such as C4 and PEG linkers have shown promise in preclinical studies, inspiring us to expand the chemical toolbox for enhanced therapeutic performance and mechanistic insight.
Oligonucleotides interact with various cellular proteins and can trigger immune responses, affecting their efficacy, delivery, and safety. Using structural probes, we aim to unravel these complex interactions and inform the rational design of next-generation therapies.
We design oligonucleotides to address a broad spectrum of rare genetic disorders, including repeat expansion diseases such as Huntington’s disease, where targeting CAG repeats can delay onset, and non-repeat-associated conditions. Our research encompasses the development of oligonucleotide therapies for both neurological and non-neurological diseases, including disorders that affect the brain, heart, and other organs, to expand treatment options for patients with unmet medical needs.
While GalNAc conjugation has revolutionized liver-targeted oligonucleotide delivery, targeting other tissues remains a significant challenge. We are developing novel ligand conjugates—including sugars, antibodies, and peptides—to deliver therapeutics precisely beyond the liver.
If you are interested in joining the O’Reilly Lab at UTMB to work on cutting-edge oligonucleotide therapeutics for rare and ultra-rare diseases, we welcome highly motivated and enthusiastic volunteers and recruits with a willingness to learn.
