Internal Reference: 2026-003

Market Need 

Chemically modified small interfering RNA (siRNA), antisense oligonucleotides (ASOs), and messenger RNA (mRNA) therapeutics offer major advantages over traditional small‑molecule drugs, including rapid development timelines, long durations of action, and the ability to modulate or express virtually any gene or protein. However, their widespread therapeutic adoption has been limited by shared challenges inherent to large, negatively charged nucleic acids, particularly their poor stability, inefficient delivery to mammalian cells, and—especially for siRNAs and ASOs—the extremely low (<1%) escape of oligonucleotides from endosomal vesicles into the cytoplasm, which severely reduces potency. For mRNA, these same molecular properties also hinder cellular uptake and contribute to short intracellular lifetimes. Delivery and intracellular trafficking can be improved by coupling nucleic acids to carriers such as antibodies via chemical linkers, but previously used non‑cleavable linkers have introduced significant barriers across multiple modalities: in siRNA and ASO conjugates, they impede endosomal escape and suppress gene‑silencing activity, while in mRNA systems, they can block translation, particularly when incorporated within the open reading frame, thereby limiting the therapeutic potential of these otherwise highly versatile nucleic‑acid‑based drugs.

Technology Overview

¾ÅÉ«ÊÓƵ has developed endosome‑reversible, pH‑sensitive linkages that enable highly efficient conjugation of mRNA, siRNAs, and antisense oligonucleotides (ASOs) to molecular carriers. Following cellular uptake through receptor‑mediated endocytosis, these novel linkages are rapidly and efficiently cleaved within late endosomes, releasing fully active nucleic acids—including siRNAs, ASOs, and mRNA—into the cytoplasm.

Commercial Advantages

• Cell-type-selective targeting of the conjugates can be tuned by choosing different carrier moieties such as antibodies, lipids, aptamers, or FDA-approved small-molecule drugs — which, upon release, can also mediate additional pharmacological effects.
• The resulting products can be isolated in high purity and demonstrate potent and selective expression of proteins upon delivery into cells.
• The conjugation reaction between the modified oligonucleotide and carrier is highly efficient and fully compatible with clinically validated chemical modifications present in therapeutic oligonucleotides.
• Modified mRNAs can be synthesized using standard in vitro transcription, producing high-purity products that can be conjugated to virtually any aldehyde- or ketone-containing carrier molecule or small-molecule drug.

Additional Information

• Researcher: Nathan Luedtke
• ±Ê²¹³Ù±ð²Ô³Ù²õ:ÌýUSÌý±Ê°ù´Ç±¹¾±²õ¾±´Ç²Ô²¹±ôÌý(¹ó¾±±ô±ð»å)
• Keywords: Composition of Matter, Gene Therapy, Therapeutic