Modified Amine Lipids for CRISPR Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current compositions for delivering CRISPR/Cas gene editing components, such as mRNA encoding the CRISPR protein component and CRISPR guide RNAs, into cells are inadequate for effective in vitro and in vivo delivery.
Innovation Solution
The use of amine-containing lipids to formulate lipid nanoparticle (LNP) compositions that facilitate the delivery of CRISPR/Cas gene editing components into cells, specifically through the formulation of compounds according to structures such as Formula (IA) and (I).
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional delivery compositions are used, then delivery of CRISPR/Cas components to cells is attempted, but delivery effectiveness is inadequate
Solution Approach 1:
The patent modifies the chemical structure of ionizable lipids by changing parameters such as the hydrophobic region (varying carbon chain lengths and unsaturation), the hydrophilic region (different amine groups and linkers), and the overall molecular weight. These parameter changes optimize the lipid's ability to form LNPs and deliver CRISPR/Cas components effectively into cells, resolving the contradiction between delivery reliability and gene editing efficiency
Solution Approach 2:
The patent creates composite lipid structures combining hydrophobic fatty acid chains with hydrophilic amine-containing head groups. These composite ionizable lipids self-assemble with nucleic acids to form lipid nanoparticle complexes that effectively deliver CRISPR/Cas components into cells, transforming the inadequate conventional delivery into effective gene editing delivery
2Reliability
If LNP compositions are formulated with modified ionizable lipids, then delivery effectiveness is improved, but lipid structure complexity increases
Solution Approach 1:
The ionizable lipids are segmented into distinct functional regions: a hydrophobic fatty acid region (with specific chain lengths and unsaturation levels) and a hydrophilic amine-containing head group region (with specific linkers and basic groups). This segmentation allows each region to perform its specific function optimally while maintaining overall molecular manageability, improving delivery effectiveness without excessive complexity
Solution Approach 2:
The ionizable lipid structure is designed to perform multiple functions: forming amphipathic structures for membrane interaction, self-assembling with nucleic acids into LNPs, facilitating cellular uptake, and enabling endosomal escape. This multi-functionality is achieved through a unified molecular design that combines hydrophobic and hydrophilic regions with specific amine groups, improving delivery effectiveness while avoiding unnecessary structural complexity
Data Source
AI summary
The disclosure provides ionizable amine lipids and salts thereof (e.g., pharmaceutically acceptable salts thereof) useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The ionizable amine lipids disclosed herein are useful as ionizable lipids in the formulation of lipid nanoparticle-based compositions.