Delivery of Oligonucleotides

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention provides an improved method for delivering antisense oligonucleotides (EONs) designed for site-specific RNA editing inside cells. It leverages a specific plant-derived triterpene glycoside, AG1856 (isolated from Agrostemma githago L.), as a delivery enhancer, either by co-administration or direct conjugation to the therapeutic oligonucleotide. This enhancement significantly increases the ability of the EONs to enter cells and induces the recruitment of the cell's own ADAR enzyme, which specifically edits target adenosines in RNA, converting them to inosines for therapeutic benefit.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment of genetic disorders caused by point mutations or single nucleotide variants, such as Hurler syndrome, hemochromatosis, Duchenne muscular dystrophy, and more
• Therapeutic RNA editing of genes involved in cardiovascular, liver, kidney, pancreatic diseases, or central nervous system disorders
• Correction of disease-related RNA sequences in patient cells either in vivo or ex vivo (e.g., gene therapy for inherited diseases)
• Efficient delivery of antisense oligonucleotide therapeutics for research or diagnostic purposes, especially where high cell uptake is challenging
• Engineering or regulating protein function by specific post-transcriptional RNA editing

BenefitsContent extracted from patent full text and abstract with AI.

• Significantly enhances cellular uptake and endosomal escape of therapeutic oligonucleotides, reducing required dosage and potential toxicity
• Enables high-efficiency, specific RNA editing without the need for exogenous enzymes or genetic modification of the target cell (uses endogenous ADAR)
• Can deliver modified and stabilized EONs with increased resistance to degradation, improving therapeutic stability and effect
• Demonstrated efficacy in multiple tissue types and across both in vitro and in vivo models, supporting broad applicability
• Versatile delivery: can be used as a directly conjugated molecule or as part of a two-component kit, offering dosing flexibility
• Potential for nearly complete RNA editing in target cells, thus high therapeutic efficiency
• Expands the applicability of RNA editing therapeutics to diverse and clinically relevant disease gene targets

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The invention relates to the field of medicine and to the field of RNA editing, wherein a target adenosine present in a target RNA molecule in a cell is deaminated to an inosine by an endogenous ADAR enzyme that is recruited by a double-stranded complex generated between an administered RNA editing producing antisense oligonucleotide (EON) and a region of the target RNA molecule that comprises the target adenosine. The invention relates to the improved delivery of the EON to the target cell using a triterpene glycoside purified from seeds of Agrostemma githago L.