Dendritic Cell-Targeting Lipid Nanoparticles With Glycan-Lipid Conjugates
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Solution Overview
Problem
Existing lipid nanoparticles lack selective delivery functionality, leading to inefficient targeting of specific cell types such as dendritic cells, and their manufacturing can be costly.
Innovation Solution
A bi-functional compound with a glycan-based cell-targeting moiety and lipid moiety is incorporated into lipid nanoparticles to enhance selective delivery, specifically targeting dendritic cells by binding to receptors like DC-SIGN, Siglec-1, Siglec-2, or Siglec-5/E, and includes a spacer for structural flexibility and improved binding affinity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional lipid nanoparticles are used for delivery, then the delivery system is simple and cost-effective, but the delivery lacks selective functionality and cannot efficiently target specific cell types such as dendritic cells
Solution Approach 1:
The patent merges a targeting moiety (such as a carbohydrate, peptide, or antibody fragment) with a lipid nanoparticle formulation to create a bi-functional nanoparticle. This combination integrates the delivery capability of the lipid nanoparticle with the selective binding capability of the targeting moiety, enabling efficient targeting of dendritic cells while maintaining the overall nanoparticle structure and function.
Solution Approach 2:
The targeting moiety is designed to perform multiple functions: it provides selective binding to dendritic cell surface markers (such as DC-SIGN, Siglec-1, Siglec-2, or Siglec-5/E), facilitates cellular uptake, and can enhance the delivery of therapeutic payloads. This multi-functionality addresses the selective delivery requirement without requiring separate components for each function.
2Manufacturing precision
If conventional lipid nanoparticles are used, then manufacturing is cost-effective, but they cannot provide localized selectivity and require fine-tuning of lipid ratios
Solution Approach 1:
The nanoparticle system is segmented into distinct functional components: the lipid nanoparticle core for delivery and the targeting moiety for selectivity. This segmentation allows each component to be optimized and manufactured separately, then assembled together, simplifying the overall manufacturing process while achieving precise targeting functionality.
Solution Approach 2:
The patent modifies the surface properties of the nanoparticle by incorporating targeting moieties with specific binding affinities. This parameter change in surface functionality enables localized selectivity without fundamentally altering the core lipid nanoparticle formulation or manufacturing process, maintaining ease of manufacture while improving targeting precision.
3Reliability
If conventional lipid nanoparticles are used for mRNA delivery, then the system is stable and protective, but it lacks selective delivery capability and cannot efficiently deliver to dendritic cells
Solution Approach 1:
The patent combines the protective and stable lipid nanoparticle formulation with a targeting moiety that specifically recognizes dendritic cell surface markers. This merging enables the nanoparticle to maintain its protective function while gaining the ability to efficiently deliver to and be taken up by dendritic cells, addressing the cellular uptake efficiency requirement.
Solution Approach 2:
The targeting moiety acts as an intermediary between the nanoparticle and the dendritic cell surface receptors. It facilitates the interaction by providing specific binding to markers such as DC-SIGN, Siglec-1, Siglec-2, or Siglec-5/E, thereby enhancing cellular uptake efficiency without requiring fundamental changes to the nanoparticle or cell biology.
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 novel nanoparticle formulation demonstrates enhanced uptake and transfection efficiency in dendritic cells, inducing immune responses and providing targeted delivery of therapeutic agents or immunogenic biomolecules.
Implementation Method 1
targeting dendritic cells by binding to receptors like DC-SIGN, Siglec-1, Siglec-2, or Siglec-5/E
Implementation Method 2
lipid nanoparticles (LNP) were developed to encapsulate and stabilize mRNA molecules
Data Source
AI summary
The present disclosure relates to novel compounds, methods, and cell-targeting formulations, e.g., a lipid nanoparticle (LNP) for targeted delivery to a tissue or a cell type. The compound and formulation provided herein are designed to have a targeting moiety configured to provide selective delivery features for the formulation and a lipid tail for being incorporated into the bilayer membrane of the formed lipid nanoparticle.