SNA2026: The Third Small Nucleic Acid Drug R&D and Industrialization Forum – Entering the Golden Era of a Next-Generation Therapeutic Modality

Lecture Topic:

Oligonucleotide Drug Development Moves Toward a Blue Ocean

Lecture Summary:

(1) Traditional undruggable targets are the focus of differentiated competition for small nucleic acid drugs 

(2) Overcome bottleneck technologies to exert effects in a broader range of target organs and tissues

(3) Addressing Unmet Clinical Needs and Pioneering New Frontiers in CNS and Metabolic Diseases

Lecture Topic:

Principles and Clinical Progress of Stano Therapeutics' Small Interfering RNA Nanoparticles for Localized Fat Reduction

Lecture Summary:

STP705 is a small interfering RNA (siRNA) nanoparticle developed by Starna Therapeutics, with its safety and efficacy validated in Phase I clinical trials. Today, we will share its mechanism of action and clinical progress data.

Lecture Topic:

A Brief Analysis of Quality Control for Oligonucleotide Drugs

Lecture Summary:

(1) Research and Development Progress and Guiding Principles for Oligonucleotide Drugs

(2) Quality Standards and Analytical Methods for Oligonucleotide Drugs

(3) Impurity Studies of Oligonucleotide Drugs

Lecture Topic:

Research on miRNA-like Off-target Effects of siRNA and Sharing of Application Cases

Lecture Summary:

（1）Comparison of the Mechanisms of Action of siRNA and miRNA.

（2）miRNA-like Off-target Effects of siRNA

（3）Case Study Analysis

Yang Zhenjun

Professor, School of Pharmaceutical Sciences, Peking University Health Science Center; Principal Investigator, State Key Laboratory of Natural and Biomimetic Drugs

Lecture Topic:

Research on In Vivo Targeted Delivery of Novel Nucleic Acid Drug Lipid Nanoparticle Formulations

Developed a novel nanocarrier system combining nucleoside/nucleotide lipids with cystine-based cationic lipids. This system binds to nucleic acid therapeutics via hydrogen bonding, π-π stacking, and electrostatic interactions, enters cells through non-lysosomal pathways, and enables significant nuclear uptake for certain formulations. By optimizing the lipid composition ratios and incorporating grafts such as DSPE-PEG(-cRGD), we controlled the particle size and surface charge of the lipid complexes. This yielded nanocarriers with excellent in vivo disease tissue distribution and pharmacokinetic properties, characterized by high efficiency, low toxicity, and suitability for intravenous administration. The system achieves efficient in vivo (targeted) delivery of various (oligo)nucleotides (including siRNA, antisense oligonucleotides, aptamers, cyclic dinucleotides, and mRNA) and their modified or conjugated forms. It demonstrated significant safety and therapeutic efficacy in mouse models of liver cancer, pancreatic cancer, and cervical cancer. Notably, the formulation’s nuclear distribution was found to exert tumor-suppressive and other therapeutic effects at multiple stages. Furthermore, computer simulations of these nanoparticles were conducted. Referencing experimental results and small molecule-protein interaction data, an AI-based model for predicting protein corona composition was established to elucidate the mechanisms underlying organ-targeted delivery.