• Adenosine ribonucleoside molecule. Chemical structure and molecule model of nucleoside.
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O'Reilly Lab

Genetic Medicines: Transforming the Future of Rare Diseases

About Our Lab

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.

Therapeutic Platforms:

We leverage three main classes of oligonucleotide therapeutics:

  • Antisense Oligonucleotides (ASO): Bind to RNA to modulate splicing or degrade mRNA, preventing the production of harmful proteins.
  • Short interfering RNA (siRNA)s: Silence target genes by promoting degradation of specific mRNA which prevents the production of harmful proteins.
  • CRISPR: Enables precise editing of disease-causing genes at the DNA level.

Our Approach

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.

Research Areas

Novel Chemical Modifications

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.

Adenosine ribonucleoside molecule. Chemical structure and molecule model of nucleoside.

Oligonucleotide Chemical Biology

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.

Chemistry lab icon set. Included icons as Chemical, formula, Medical analysis, Laboratory test flask.

Rare Disease Therapeutics

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.

Rare Disease Day Background. Colorful awareness ribbon with group of people with rare diseases.

Tissue-Specific Delivery

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.

Visual scheme of the structure of man and human organs.

Meet the Team

Portrait of Sabina Dahal,
Email: sadahal@UTMB.EDU
Sabina Linkedin

Sabina Dahal

Lab Technician

About Me

Sabina Dahal is a Research Technician at the University of Texas Medical Branch (UTMB), where she contributes to the development of innovative genetic medicines for rare genetic diseases. She earned her Bachelor of Science degree in Biology (Molecular Biology & Biotechnology) from the University of Louisiana Monroe (ULM), where she discovered her passion for exploring new therapeutics to address cancer and rare diseases.

Sabina began her research journey as an Emerging Scholar at ULM and went on to complete three consecutive Louisiana Biomedical Research Network (LBRN) summer internships. During this time, she conducted drug discovery research focused on overcoming challenges such as drug resistance in cancer, working at the intersection of biology and chemistry. She presented her work at multiple scientific conferences and received a travel award from the Louisiana Cancer Research Center. She loves to connect with other scientists to exchange ideas and gain new insights into the broader implications of her findings.

Her academic and research experiences reflect her dedication to advancing health through innovation and collaboration. Sabina is especially motivated by the potential of genetic medicines to transform patient care and aspires to pursue a Ph.D. in Biomedical Sciences in the future. Outside the lab, she enjoys traveling, exploring new cultures, and engaging in mentorship and outreach that inspire the next generation of scientists.

Email: sadahal@UTMB.EDU
Sabina Linkedin

Publications

Divalent siRNAs are bioavailable in the lung and efficiently block SARS-CoV-2 infection

Hariharan, V. N., Shin, M., Chang, C. W., O’Reilly, D., Biscans, A., Yamada, K., Guo, Z., Somasundaran, M., Tang, Q., Monopoli, K., Krishnamurthy, P. M., Devi, G., McHugh, N., Cooper, D. A., Echeverria, D., Cruz, J., Chan, I. L., Liu, P., Lim, S. Y. & McConnell, J. & 26 others, Singh, S. P., Hildebrand, S., Sousa, J., Davis, S. M., Kennedy, Z., Ferguson, C., Godinho, B. M. D. C., Thillier, Y., Caiazzi, J., Ly, S., Muhuri, M., Kelly, K., Humphries, F., Cousineau, A., Parsi, K. M., Li, Q., Wang, Y., Maehr, R., Gao, G., Korkin, D., McDougall, W. M., Finberg, R. W., Fitzgerald, K. A., Wang, J. P., Watts, J. K. & Khvorova, A., Mar 10 2023, In: Proceedings of the National Academy of Sciences of the United States of America. 120, 11, e2219523120.

Research output: Contribution to journal › Article › peer-review

Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington's disease

O'Reilly, D., Belgrad, J., Ferguson, C., Summers, A., Sapp, E., McHugh, C., Mathews, E., Boudi, A., Buchwald, J., Ly, S., Moreno, D., Furgal, R., Luu, E., Kennedy, Z., Hariharan, V., Monopoli, K., Yang, X. W., Carroll, J., DiFiglia, M. & Aronin, N. & 1 others, Khvorova, A., Jun 7 2023, In: Molecular Therapy. 31, 6, p. 1661-1674 14 p.

Research output: Contribution to journal › Article › peer-review

Erratum: Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington's disease (Molecular Therapy (2023) 31(6) (1661–1674), (S1525001623002629), (10.1016/j.ymthe.2023.05.006))

O'Reilly, D., Belgrad, J., Ferguson, C., Summers, A., Sapp, E., McHugh, C., Mathews, E., Boudi, A., Buchwald, J., Ly, S., Moreno, D., Furgal, R., Luu, E., Kennedy, Z., Hariharan, V., Monopoli, K., Yang, X. W., Carroll, J., DiFiglia, M. & Aronin, N. & 1 others, Khvorova, A., Nov 1 2023, In: Molecular Therapy. 31, 11, p. 3355-3356 2 p.

Research output: Contribution to journal › Comment/debate › peer-review

Complete list of publications 

Join our team

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.