Binding-Moiety Nucleic Acid Conjugates for Intracellular Uptake
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Solution Overview
Problem
Nucleic acid therapies face challenges such as poor intracellular uptake, limited blood stability, and non-specific immune stimulation, hindering their effectiveness in targeted gene suppression and disease treatment.
Innovation Solution
Development of oligonucleotide conjugates comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer, arranged in specific configurations to enhance intracellular uptake, stability, and reduce toxicity and non-specific immune stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acid therapies are used for targeted gene suppression, then therapeutic efficacy is improved, but intracellular uptake is poor
Solution Approach 1:
The patent employs binding moieties (such as antibodies, protein conjugates, or peptide nucleic acids) as intermediary carriers that facilitate intracellular delivery of nucleic acid therapies. These binding moieties interact with cellular transport mechanisms to improve uptake while maintaining the therapeutic function of the nucleic acid component.
Solution Approach 2:
The invention creates composite conjugate molecules combining nucleic acid components with binding moieties and polymers. This composite structure integrates the therapeutic properties of nucleic acids with the delivery capabilities of binding moieties, achieving both improved intracellular uptake and maintained therapeutic efficacy.
2Reliability
If nucleic acid therapies are administered, then targeted gene suppression is achieved, but blood stability is limited
Solution Approach 1:
Polymers serve as intermediary stabilizing agents that conjugate to nucleic acid therapies, protecting them from degradation in the bloodstream. These polymer conjugates extend circulation half-life and maintain blood stability while preserving the nucleic acid's ability to suppress target genes.
Solution Approach 2:
The patent modifies physical and chemical parameters of nucleic acid therapies through conjugation with binding moieties and polymers, changing their molecular weight, charge distribution, and structural conformation to improve blood stability and circulation characteristics.
3Reliability
If nucleic acid therapies are used, then gene suppression effectiveness is improved, but non-specific immune stimulation occurs
Solution Approach 1:
The binding moieties and polymers are designed with specific local properties that distinguish the conjugate from endogenous immune triggers. The conjugate structure incorporates regions of low immunogenicity while maintaining the nucleic acid's target-specific binding capability, thereby reducing non-specific immune stimulation.
Solution Approach 2:
The binding moieties act as intermediary structures that shield the nucleic acid from direct immune recognition. These moieties can be selected or engineered to have low immunogenicity, serving as a protective interface between the nucleic acid therapy and the immune system.
Data Source
AI summary
Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.