Polyphosphoester Polymers for Nucleic Acid Delivery
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Solution Overview
Problem
The delivery of nucleic acids as therapeutics remains a challenge due to inefficiencies in existing delivery methods, particularly in achieving safe and potent delivery of nucleic acids across cellular barriers.
Innovation Solution
Development of specific polymers with a repeating unit structure that enhances endosomal release and biodegradability, allowing for safer and more effective delivery of nucleic acids, such as mRNA, by forming a polymer composition that includes a repeating unit with specific alkyl or protonatable groups, facilitating efficient cellular uptake and release of the nucleic acid payload.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional polymers are used for nucleic acid delivery, then delivery efficiency is limited, but polymer structure complexity is reduced
Solution Approach 1:
The patent modifies polymer parameters by incorporating specific functional groups (protonatable groups with pKa 6-10, endosomal release groups) and controlling molecular weight (10-60 kDa) to enhance nucleic acid delivery efficiency while maintaining manageable structural complexity
Solution Approach 2:
The patent creates composite polymer structures combining multiple functional moieties (cationic groups for binding, endosomal release groups for escape, PEG chains for stability) within a single delivery vehicle to achieve superior delivery performance
2Productivity
If non-biodegradable polymers are used for delivery, then delivery potency is improved, but patient tolerability deteriorates
Solution Approach 1:
The patent changes the biodegradability parameter of the polymer by incorporating hydrolyzable bonds (ester, amide, carbamate linkages) and controlling the polymer composition to balance delivery potency with biodegradability, ensuring the polymer degrades into safe byproducts after delivery
Solution Approach 2:
The patent designs the polymer as a temporary delivery vehicle that performs its function and then degrades, analogous to disposable materials, eliminating long-term toxicity concerns associated with persistent non-biodegradable polymers
3Object-affected harmful factors
If polymers lack endosomal release capability, then delivery safety is improved, but endosomal release efficiency deteriorates
Solution Approach 1:
The patent changes the chemical parameters of the polymer by incorporating endosomal release groups (acid-labile bonds, pH-sensitive moieties) that respond to endosomal conditions, enabling controlled release while maintaining safety through targeted activation
Solution Approach 2:
The patent introduces dynamic responsiveness to pH changes in the endosome, allowing the polymer to transition from a stable delivery vehicle in circulation to an active release mechanism upon endosomal uptake, achieving both safety and efficiency
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The polymers provide enhanced endosomal release and biodegradability, leading to more potent and safer delivery of nucleic acids, potentially treating various diseases by ensuring effective cellular uptake and release of therapeutic nucleic acids.
Implementation Method 1
The polymers of the present invention may provide enhanced endosomal release of the nucleic acid being delivered by the polymer. Additionally, the biodegradable nature of the polymer may provide greater patient tolerability than other polymeric delivery vehicles.
Data Source
AI summary
Disclosed are polymers comprising the moiety A, which is a moiety of formula I: and pharmaceutically acceptable salts thereof, wherein R, R1, R2, L, n1 and n2 are as defined herein. These polymers are useful for delivering nucleic acids to subject. These polymers and pharmaceutically acceptable compositions comprising such polymers and nucleic acids can be useful for treating various diseases, disorders and conditions.