Date: February 13, 2025
Time: 11-12pm EST
Join us for this Trainee Spotlight webinar featuring trainees Edwin van Oosten, Josh Robinson, and Trishalina Das, all of whom won poster awards at the 2024 OTS Annual Meeting.
Title: Exploring Nucleic Acid Nano-assemblies as Delivery Vehicles
Presentation Description:
Our lab has developed a type of Spherical Nucleic Acid (SNA), which is made up of a single sequence-controlled polymer. In the presence of a magnesium-containing buffer, this single strand self-assembles into discrete nano-assemblies. In this talk, I will discuss their potential as delivery vehicles for nucleic acid based therapeutics.
Speaker:
Title: Personalized ASO screening for a Stargardt disease patient carrying the deep-intronic ABCA4 variant.
Presentation Description:
Stargardt disease (STGD1) is a genetic retinal disorder caused by pathogenic variants in the ABCA4 gene, leading to vision loss. In the Collin-Garanto group at the Radboudumc, in collaboration with the Dutch Center for RNA Therapeutics (DCRT), we are developing a personalized trial for a single STGD1 patient carrying the ultrarare c.859-506G>C ABCA4 variant. We screened several antisense oligonucleotides (ASOs) using in vitro models, including patient-derived retinal organoids, in order to successfully restore ABCA4 expression. Our results revealed two lead candidate ASOs that safely and effectively restored ABCA4 expression and will be further developed therapies to treat ultrarare ABCA4 variants.
Speaker:
Title: Novel 3-Component Zwitterionic Amino Lipid Nanoparticles for mRNA Delivery
Presentation Description:
Lipid nanoparticles (LNPs) are an effective and broad class of delivery vehicles for genetic cargo. We report the synthesis of novel zwitterionic amino lipids (ZALs), a class of delivery materials that has shown efficacy for mRNA delivery. ZALs were designed to combine the chemistry of the ionizable amino lipid and the zwitterionic phospholipid into a single molecule to allow formulation of 3-component LNPs with enhanced molecular interactions between the amphipathic lipids and mRNA molecules in water pockets within the LNP. We systematically investigated the secondary hydroxyl position within ZA3-Ep10, a lead ZAL that emerged from the initial high-throughput screen as being able to effectively deliver mRNA in vitro and in vivo. Derivation of ZA3-Ep10 elucidated that chemistry indeed affects mRNA delivery efficacy as seen in a novel ZAL. Furthermore, formulation compositions were systematically modified to garner the impact of structural chemistry and composition on LNP physical and delivery characteristics.
