Lipid Nanoparticle CAR Gene Delivery Without Viral Vectors
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Solution Overview
Problem
Current CAR-T cell therapy is costly due to high cell culture and viral vector production costs, and there is no efficient method for in vivo or ex vivo introduction of CAR or exogenous TCR into immunocytes using lipid nanoparticles.
Innovation Solution
Lipid nanoparticles comprising a nucleic acid encoding CAR or exogenous TCR, cationic lipid, and non-cationic lipid, with a targeted ligand for T cells, enable selective introduction of CAR or exogenous TCR into immunocytes in vivo or ex vivo.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If viral vectors are used for CAR-T cell production, then transfection efficiency is improved, but production cost increases and viral residue testing is required
Solution Approach 1:
The patent replaces expensive viral vectors with inexpensive lipid nanoparticles containing plasmid DNA. The lipid nanoparticles are disposable, non-replicating carriers that deliver genetic material without requiring costly viral production, cell culture facilities, or viral residue testing, thereby dramatically reducing production costs while maintaining transfection capability
Solution Approach 2:
The patent uses plasmid DNA copies instead of viral vectors. The plasmid DNA contains the CAR gene and is delivered via lipid nanoparticles, creating a non-viral copy system that avoids the need for viral replication, purification, and testing while achieving the same transfection function
2Reliability
If ex vivo CAR-T cell production is performed, then therapeutic effect is achieved, but production cost and time increase
Solution Approach 1:
The patent performs CAR gene delivery directly into T cells in vivo or ex vivo using lipid nanoparticles, eliminating the need for time-consuming viral vector production and cell culture procedures. The lipid nanoparticles can be administered directly to patients or to isolated T cells, achieving rapid CAR expression without prolonged production cycles
Solution Approach 2:
The patent extracts and eliminates the time-consuming steps of viral vector production, cell culture maintenance, and viral residue testing from the CAR-T cell production process. By using lipid nanoparticles with plasmid DNA, the method removes these unnecessary intermediaries and achieves direct gene delivery, significantly reducing production time
3Reliability
If viral vectors are used for gene delivery, then transfection is achieved, but antigenicity and safety concerns increase
Solution Approach 1:
The patent extracts and removes viral proteins and viral genetic material from the gene delivery system. By using lipid nanoparticles containing only plasmid DNA, the method eliminates all viral components that would cause antigenicity or safety concerns, while maintaining the ability to deliver and express the CAR gene
Solution Approach 2:
The patent replaces persistent viral vectors with transient, non-replicating lipid nanoparticles. The lipid nanoparticles do not integrate into the host genome, do not produce viral proteins, and are metabolized quickly, thereby eliminating long-term antigenicity and safety concerns associated with viral vectors
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
This approach allows for low-cost CAR- or TCR-immunocell therapy by avoiding the use of viral vectors and reducing antigenicity, with efficient expression of CAR or exogenous TCR in immunocytes.
Implementation Method 1
Lipid nanoparticles comprising a nucleic acid encoding CAR or exogenous TCR, cationic lipid, and non-cationic lipid
Implementation Method 2
enable selective introduction of CAR or exogenous TCR into immunocytes in vivo or ex vivo
Data Source
AI summary
The present invention provides a lipid nanoparticle containing the following (a) to (c):(a) a nucleic acid encoding a chimeric antigen receptor (CAR) or an exogenous T cell receptor (TCR);(b) a cationic lipid; and(c) a non-cationic lipid.The present invention also provides a CAR- or exogenous TCR-expressing immunocyte obtained by introducing the lipid nanoparticle into in vivo or ex vivo T cells, and an in vivo or ex vivo therapeutic approach using the immunocytes for disease such as cancer and the like.