Targeted Nucleic Acid Particles for Precise T-Cell Delivery
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Solution Overview
Problem
Current methods for delivering nucleic acids to specific cells, such as immune effector cells, lack precision and specificity, leading to potential adverse effects on non-targeted cells and inefficient treatment outcomes.
Innovation Solution
The use of particles comprising a nucleic acid payload and a targeting compound, where the targeting compound includes a hydrophobic moiety and a binding moiety covalently attached for direct or indirect targeting to cell surface antigens, allowing precise delivery of nucleic acids to immune effector cells, such as CD3+, CD4+, or CD8+ T cells, using antibodies or antibody-like molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional nucleic acid delivery methods are used, then delivery can be achieved, but precision and specificity to target cells are insufficient, causing adverse effects on non-targeted cells
Solution Approach 1:
The delivery system is segmented into distinct functional components: a particle core for nucleic acid encapsulation, a hydrophobic moiety for particle incorporation, and a binding moiety for specific cell targeting. This segmentation allows each component to be optimized independently for its specific function while working together to achieve precise targeted delivery.
Solution Approach 2:
The binding moiety acts as an intermediary that mediates between the delivery particle and the target cell. It specifically recognizes and binds to cell surface antigens on target cells, serving as a bridge that directs the nucleic acid payload to the intended destination while avoiding non-targeted cells.
2Productivity
If conventional delivery methods are used, then broad distribution is achieved, but treatment efficacy is reduced due to lack of specificity
Solution Approach 1:
The delivery system exhibits local quality by concentrating the binding function at the particle surface through the binding moiety, while the particle core maintains nucleic acid encapsulation properties. This localized functional differentiation enables specific interaction with target cells while preserving the delivery capability, thereby enhancing treatment efficacy through precise cellular targeting.
3Ease of manufacture
If non-targeted delivery is used, then simpler methods are available, but genetic modification efficiency of specific immune effector cells is low
Solution Approach 1:
The particle system achieves multi-functionality by combining nucleic acid encapsulation, cellular uptake facilitation, and specific cell targeting in a single platform. The particle can deliver different nucleic acid payloads (DNA, RNA, mRNA) to different cell types by simply changing the binding moiety, maintaining ease of use while dramatically improving genetic modification efficiency of specific immune effector cells.
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 enables selective and efficient genetic modification of immune effector cells to express antigen receptors like CAR or TCR, minimizing harm to non-targeted cells and enhancing the efficacy of disease treatment by targeting diseased cells expressing specific antigens.
Implementation Method 1
a hydrophobic moiety for incorporation into the particles
Implementation Method 2
the binding moiety of the targeting compound binds to a cell surface antigen on a target cell
Data Source
AI summary
The invention relates to agents and methods for targeted delivery of nucleic acids to cells. In some embodiments, the nucleic acid payload comprises a nucleic acid encoding an antigen receptor such as a T cell receptor (TCR) or chimeric antigen receptor (CAR). The agents and methods for targeted delivery of a nucleic acid encoding an antigen receptor described herein may be used for generating in vitro/ex vivo or in vivo immune effector cells genetically modified to express an antigen receptor.