We developed a fully chemically modified, GalNAc-conjugated oligonucleotide platform that recruits endogenous ADAR for precise A-to-I RNA editing. Targeting SERPINA1  to correct the PiZZ mutation in AATD, we achieved >90% in vitro and >50% in vivo editing, restoring therapeutic M-AAT levels with subcutaneous dosing. NHP studies showed extended half-life and no toxicity, supporting a safe, durable, disease-modifying therapy and rapid expansion to other genetic diseases.

At Orbital Therapeutics, we are pioneering circular RNA (circRNA) therapies delivered by targeted lipid nanoparticles (LNPs) for in vivo CAR T cell generation. Our innovative approach is poised to enable patients’ own immune cells to be reprogrammed directly in the body, using the high stability and durable expression of circRNA for precise, long-lasting therapeutic effects. Our technology aims to simplify and broaden access to CAR T treatments for cancer and autoimmune diseases, reducing the need for complex procedures and intensive preconditioning.

The emergence of mRNA modality as a therapeutic alternative for treatment of viruses, infectious disease, and more has highlighted the need for understanding how the design of mRNA impacts functionality of mRNA. To understanding how mRNA design impacts translation one needs to correlate the physical characterization to functional characterization of mRNA. We will discuss various strategies for assessing the impact of mRNA design on physical and functional characterization of mRNA.

Utilizing combinatorial screens we can optimize mRNA molecules to improve both durability and translation of their payloads. The easily programable nature of xRNA enables us to combine multiple payloads, generating a highly modular single backbone, that synchronizes the expression of multiple therapeutic proteins.

• Defining what properties are most important to optimize. Are there trade-offs?
• Optimizing innovative chemistries and modifications
• Strategies for regulating mRNA expression
• Addressing biodistribution, tissue specificity and safety
• Utilizing AI/ML to predict mRNA design​

• Innovative mRNA formulations and delivery approaches
• Emerging delivery vehicles, linkers and payloads for stability and targeted delivery
• Improving selectivity and efficiency of delivery
• Delivery across the blood-brain-barrier
• Targeting specific cell types for treating various diseases
• Low immunogenicity mRNA formulations​

• Innovative circular RNAs and their applications
• Optimizing tRNA design and delivery
• Case studies in cancer, autoimmune, cardiovascular, genetic disorders
• Establishing criteria for selection, application and success​

Active cellular targeting using lipid nanoparticles (LNPs) represents the next generation of RNA delivery vehicles. In my presentation, I will detail four payloads: locked nucleic acids (LNA), siRNA, mRNA, CRISPR mRNA, and sgRNAs in a single LNP. I will highlight several studies, including novel therapeutics for IBD, for hematological malignancies, for expressing a toxin protein in cancer, and for therapeutic genome editing. Special emphasis will be made on CMC challenges.

This talk will highlight RiboX Therapeutics’ proprietary plug-and-play circular RNA, ionizable lipids, and active targeting LNP platforms. It will discuss clinical updates on RXRG001, the first circular RNA therapeutic to enter clinical trials for the treatment of Radiation-Induced Xerostomia and the development of RXIM002, an in vivo generated circular RNA CAR delivered via actively targeted LNPs as an advanced therapeutic for autoimmune diseases.

mRNA therapeutics is rapidly emerging as a groundbreaking strategy for treating cardiovascular diseases (CVD), which claimed 20 million lives globally in 2022 and affects 650 million people. Despite advances in medicine, the need for curative therapies remains urgent. In my presentation, I will share a decade of our work on mRNA therapies that promote cardiac function and repair, combat fibrosis, cell death, and hypertrophy in CVD models. Additionally, we introduce novel cell-specific mRNA expression platforms, advancing the field of CVD therapeutics.