Emerging in silico tools are transforming how antisense oligonucleotide (ASO) therapies are designed for rare genetic diseases. These advances are enabling systematic evaluations of ASO efficacy, guiding researchers on rational ASO design to accelerate therapeutic development.

This talk will bring together recent advances in computational and data-driven approaches for ASO design and evaluation. We will highlight how in silico models, structured ASO datasets, and integrated preclinical data frameworks are being used to improve the prioritization, safety prediction, and overall efficiency of ASO development pipelines for rare genetic diseases.

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This talk presents an envisioned end‑to‑end CMC roadmap for N=1 oligonucleotide therapeutics, outlining the critical development steps required to progress to the clinic. We will explore how the CMC framework for oligonucleotides can be adapted to the unique challenges of ultra‑personalized candidates while maintaining quality, safety, and regulatory rigor. The session will highlight practical considerations like risk‑mitigation strategies and opportunities for streamlined development in this emerging therapeutic area.

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RNA therapeutics are coming of age. As programmable informational drugs, they offer unique opportunities for academia to develop and contribute to therapies for ultra-rare and highly innovative indications.

This talk will share our experience developing ultra-rare oligonucleotide-based therapeutics in an academic setting. Academic drug development has significant limitations, particularly budget constraints, but it also creates opportunities to challenge the status quo in CMC, IND-enabling studies, toxicology, and clinical study design. We will discuss how academic programs can ask focused questions, design cost-effective studies, and rapidly determine whether a drug is functional and worth advancing.

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Individualized medicines for patients with ultra-rare, life-threatening genetic conditions have historically been developed through singular, case by case efforts focused on one or few unique genetic variants. While this approach has enabled lifesaving treatments for individual patients, it has not generated the systematic evidence needed to support scalability, regulatory learning, or broader access to individualized therapies.

This session will describe a collaborative model in which EveryONE Medicines and Great Ormond Street Hospital (GOSH) have developed a master protocol to advance the development of individualized medicines beyond one-off compassionate use. The first patient treated under the Master Protocol represents a critical milestone demonstrating the operational feasibility of this approach. This webinar will introduce the
Master Protocol (EOM-MP1), a prospective clinical framework designed to enable standardized data collection and prespecified analyses across individualized antisense oligonucleotide (ASO) therapies for patients with unique genetic variants. By incorporating structured run-in periods, within-participant comparisons, and harmonized safety, biomarker, functional, and quality-of-life assessments, the protocol is designed to generate a robust evidence base to inform regulatory decision-making and support the
advancement of individualized medicines at scale, while preserving the flexibility required for N-of-1 therapies.

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The SPTAN1 c.6908_6916dup (p.D2303_L2305dup) variant causes severe developmental epileptic encephalopathy type 5 (DEE5) with high risks of early mortality. We investigated the molecular interactors of SPTAN1 and provided confirmatory cellular evidence of dominant-negative disease mechanism. We identified specific therapeutic targets within individuals for precision antisense oligonucleotide therapy development and are currently optimizing our candidate oligos with the goal of reducing disease burden in individuals.

Christiana Wang, BS, is a fourth-year PhD candidate in the Department of Molecular and Human Genetics at Baylor College of Medicine. She graduated summa cum laude with a Bachelor of Science in honors Biology and a minor in Data Science from Case Western Reserve University in 2021. After graduating, she joined the National Institute of Allergy and Infectious Diseases to study immunogenetic mechanisms for establishing the maternal-fetal barrier in early pregnancy. She joined Dr. Pengfei Liu’s laboratory in 2023 and spearheaded efforts to study disease mechanisms and develop translatable treatments for individuals with genetic disorders. The overarching goal of this research is to set forward a streamlined pipeline for n-of-1 therapy development and preclinical validation, helping families affected by rare genetic disorders.

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This talk will highlight the development of an individualized immunotherapy platform using oligonucleotides for solid tumors, spanning from patient sample to manufactured drug product. I will share lessons from advancing the platform through FDA interactions and early clinical studies, and explore the CMC and manufacturing challenges, as well as the risk–benefit considerations, of individualized oligonucleotide programs.

Dr. Zohar Pode is a Postdoctoral Fellow at Harvard’s Wyss Institute, working on innovative delivery platforms for oligonucleotide therapeutics. Prior to joining the Wyss, Zohar served as Head of CMC and Manufacturing Site Manager at Aummune Ltd., an immunotherapy company, where she led the development of individualized aptamer-based platforms for solid tumors, advancing from R&D to Phase I clinical trials. Her background spans both academic and industry leadership roles at the intersection of chemistry, biotechnology, and translational medicine.

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