Ractigen Therapeutics Publishes Foundational Study on its Extrahepatic LiCO™ Delivery Platform in Molecular Therapy - Nucleic Acids

• Peer-reviewed study demonstrates potent, multi-month extrahepatic delivery via both systemic administration—targeting skeletal muscle, heart, and adipose tissue—and localized routes across ocular, joint, and bladder compartments
• Unlocks high-value therapeutic tissues for neuromuscular, cardiovascular, and cardiometabolic diseases through CD36-mediated uptake, achieving ~90% target knockdown and functional muscle hypertrophy in non-human primates with only transient liver activity
• Clinically validated across both systemic and local routes of administration through ongoing clinical programs RAG-18 (systemic saRNA for Duchenne muscular dystrophy) and RAG-01 (intravesical saRNA for non-muscle invasive bladder cancer)

NANTONG, China, Oct. 23, 2026 /PRNewswire/ -- Ractigen Therapeutics, a clinical-stage biopharmaceutical company pioneering small activating RNA (saRNA) and targeted oligonucleotide therapeutics, today announced the publication of a foundational peer-reviewed study in Molecular Therapy – Nucleic Acids detailing the design, mechanism, and preclinical translation of its proprietary LiCO™ (Lipid-Conjugated Oligonucleotide) platform.

The article, titled "The LiCO Platform: A Novel Benzimidazole-Based Lipid Conjugate for Versatile and Sustained siRNA Delivery Beyond the Liver", demonstrates how a chemically defined, single-entity lipid conjugate synthesized via standard solid-phase chemistry overcomes one of the central bottlenecks in genetic medicine: achieving potent, durable oligonucleotide delivery to extrahepatic organs via both systemic and local routes of administration (ROA).

Unlocking High-Value Extrahepatic Tissues: Skeletal Muscle, Heart, and Adipose

While GalNAc conjugation has transformed liver-directed RNA therapeutics, extending oligonucleotide delivery beyond the liver has historically relied on complex lipid nanoparticles or bulky antibody and peptide conjugates that face manufacturing, tissue-penetration, or tolerability challenges. In particular, achieving safe and durable systemic delivery to skeletal muscle, cardiac tissue, and adipose tissue represents a major frontier for addressing widespread and debilitating conditions—ranging from genetic neuromuscular disorders and heart failure to obesity and cardiometabolic diseases.

Ractigen's LiCO™ platform pairs an optimized lipid moiety with a proprietary benzimidazole-based (SDL™) linker at the 5′ end of the passenger strand, markedly enhancing intracellular delivery activity while remaining fully compatible with both gene-silencing (siRNA) and gene-activating (saRNA) payloads.

Key Findings from the Molecular Therapy – Nucleic Acids Publication

• Systemic Delivery to Muscle, Heart, and Adipose with Multi-Month Durability: In mice, a single systemic dose of a LiCO-conjugated oligonucleotide achieved >90% target mRNA knockdown across skeletal muscle, heart, aorta, and adipose tissue, with ≥50% silencing persisting for at least six months and measurable activity extending to nine months. Crucially, while initial tissue distribution occurs in both liver and extrahepatic organs, hepatic activity clears rapidly, leaving a long-lived functional depot selectively within extrahepatic tissues.
• CD36-Driven Tissue Tropism: Mechanistic studies in Cd36-knockout models established the fatty acid translocase CD36 as the primary receptor mediating functional cellular uptake in muscle, heart, and adipose tissue—explaining LiCO's natural affinity for metabolically active extrahepatic organs.
• Robust Non-Human Primate (NHP) Translation: In cynomolgus macaques, two intravenous doses of LiCO-siMSTN produced ~90% myostatin (MSTN) mRNA knockdown across skeletal muscles, sustained 60–70% suppression of circulating myostatin protein through Day 98, and progressive functional muscle hypertrophy. High-resolution in situ hybridization confirmed deep parenchymal penetration into skeletal myofibers, cardiomyocytes, and vascular smooth muscle cells, accompanied by a clean clinical, hematological, and biochemical safety profile.
• Versatile Local Delivery Across Multiple Organs: Beyond systemic administration, LiCO mediated potent localized gene modulation with minimal systemic exposure across three distinct anatomical compartments: 90% target silencing in the joint synovium (intra-articular), 74% in the retina (intravitreal), and 47% in the bladder urothelium (intravesical).

Dual Clinical Validation: Systemic (RAG-18) and Local (RAG-01) Pipeline Translation

Because the LiCO™ architecture improves functional intracellular delivery across oligonucleotide classes, Ractigen has rapidly translated the platform into clinical trials validating both its systemic and local delivery capabilities:

• Systemic Clinical Validation in Muscle & Heart — RAG-18 for Duchenne Muscular Dystrophy (DMD): Directly leveraging LiCO's systemic tropism for skeletal and cardiac muscle, RAG-18 is a first-in-class LiCO-conjugated saRNA designed to transcriptionally upregulate utrophin (UTRN) to functionally compensate for dystrophin deficiency across all DMD patients regardless of mutation type. Because DMD morbidity and mortality are driven by progressive degeneration of both skeletal muscle and the myocardium, LiCO's ability to penetrate both tissues systemically provides a critical therapeutic advantage. Ractigen recently presented positive first-in-human data for RAG-18 at the 2026 World Muscle Society (WMS) Congress, establishing clinical proof-of-mechanism for systemic LiCO-enabled RNA activation in patients with DMD.
• Local Clinical Validation in the Bladder — RAG-01 for Non-Muscle Invasive Bladder Cancer (NMIBC): Building on LiCO's intravesical delivery profile demonstrated in the publication, RAG-01 is a LiCO-conjugated saRNA engineered to locally activate the tumor suppressor gene CDKN1A (p21) within bladder tumors while sparing systemic tissues. As previously presented at the European Association of Urology (EAU) 2025 Congress, RAG-01 has already demonstrated promising early complete responses (CRs) and a favorable tolerability profile in its Phase I clinical trial in patients with high-risk NMIBC.

"Skeletal muscle, cardiac tissue, and adipose tissue sit at the center of a vast spectrum of human diseases—from devastating neuromuscular and cardiovascular disorders to global metabolic syndromes—yet they have remained largely out of reach for conventional oligonucleotide chemistry," said Long-Cheng Li, M.D., Founder and CEO of Ractigen Therapeutics and senior author of the study. "Our publication in Molecular Therapy – Nucleic Acids establishes how the benzimidazole-enabled LiCO™ platform harnesses CD36-mediated uptake to unlock these high-value organs systemically, while also enabling potent local delivery to the eye, joint, and bladder. Most importantly, LiCO is already clinically validated in patients across both routes of administration: locally with early complete responses in our Phase I RAG-01 bladder cancer trial, and systemically with positive first-in-human proof-of-mechanism data for RAG-18 in Duchenne muscular dystrophy."

The full open-access article is available online in Molecular Therapy – Nucleic Acids: https://doi.org/10.1016/j.omtn.2026.103154.

About the LiCO™ Platform

LiCO™ (Lipid-Conjugated Oligonucleotide) is Ractigen's proprietary extrahepatic oligonucleotide delivery platform designed to transport double-stranded RNA therapeutics (including saRNA and siRNA) to tissues beyond the liver. Synthesized as a single chemical entity via scalable solid-phase chemistry, LiCO™ combines a proprietary benzimidazole-based (SDL) linker with an optimized lipid conjugate to harness CD36-mediated endocytosis—achieving deep tissue penetration and multi-month durability across skeletal muscle, heart, vascular smooth muscle, and adipose tissue via systemic administration, as well as potent target engagement in ocular, articular, and urothelial tissues via local administration.

About Ractigen Therapeutics

Ractigen Therapeutics is a clinical-stage biopharmaceutical company dedicated to discovering and developing transformative small activating RNA (saRNA) and siRNA therapeutics for diseases intractable to conventional modalities. Powered by its proprietary smart-TCC™ saRNA discovery engine and extrahepatic delivery platforms (LiCO™ and SCAD™), Ractigen is advancing a differentiated clinical and preclinical pipeline targeting neuromuscular, metabolic, cardiovascular, oncology, and rare genetic disorders, including clinical-stage programs RAG-01 (NMIBC), RAG-18 (DMD), and RAG-17 (SOD1-ALS). For more information, please visit www.ractigen.com, and follow us on X and LinkedIn.

SOURCE Ractigen Therapeutics