Block Copolymer Micelles for CRISPR Delivery
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Solution Overview
Problem
Current methods for combining RNAi and platinum therapies face challenges due to premature siRNA inactivation, and existing gene editing tools like CRISPR/Cas face delivery inefficiencies and off-target effects, limiting their effectiveness in cancer treatment and genetic modification.
Innovation Solution
A composition comprising a nuclease such as Cas9, TALEN, or zinc finger, optionally with a DNA editing template, and a block copolymer that non-covalently associates with the agent, along with a pharmaceutically acceptable carrier, mRNA, and guide RNA, to enhance delivery and stability of RNAi and platinum-based therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If siRNA is combined with platinum therapies, then synergistic anticancer activity is improved, but premature siRNA inactivation occurs reducing therapy effectiveness
Solution Approach 1:
The patent employs block copolymers as intermediary carriers that physically protect siRNA from platinum-induced inactivation. The copolymer forms a protective complex with siRNA, preventing direct interaction between platinum agents and siRNA while still allowing both to exert their therapeutic effects synergistically.
Solution Approach 2:
The invention creates composite delivery systems combining block copolymers with siRNA and platinum agents. This composite structure allows the siRNA to be protected within the polymer matrix while maintaining access to target genes, and enables simultaneous delivery of multiple therapeutic agents with different mechanisms of action.
2Productivity
If CRISPR/Cas9 components are delivered to achieve gene editing, then gene modification efficiency is improved, but delivery inefficiency and off-target effects limit effectiveness
Solution Approach 1:
The block copolymer acts as an intermediary delivery vehicle that facilitates cellular uptake of CRISPR/Cas9 components. The polymer carrier protects the nucleic acid components during delivery and enables efficient entry into target cells, thereby improving delivery efficiency and reducing off-target effects.
Solution Approach 2:
The block copolymer system serves multiple functions: it delivers CRISPR/Cas9 components, protects nucleic acids from degradation, facilitates cellular uptake, and enables precise gene editing. This multi-functional platform addresses multiple limitations of current gene editing delivery methods simultaneously.
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 solution prevents premature siRNA inactivation, maximizes synergistic activity of RNAi and platinum therapies, and improves the efficiency and specificity of gene editing by facilitating effective intracellular delivery and reducing off-target effects.
Implementation Method 1
a block copolymer comprising: (i) a first block comprising a plurality of first monomers, wherein each first monomer is hydrophilic; (ii) a second block comprising a plurality of second monomers, wherein each second monomer is hydrophobic; and (iii) a third block comprising a plurality of third monomers, wherein each third monomer is positively charged at a pH from about 6.8 to about 7.4, wherein the agent is non-covalently associated with the block copolymer
Data Source
AI summary
Disclosed are copolymer micelles for simultaneous delivery of Cas9 mRNA and guide RNA for Cas9 CRISPR gene editing. Also disclosed are copolymer micelles for simultaneous delivery of a therapeutic or diagnostic nucleic acid and a cross-linking or alkylating anticancer agent.