Modified Cell Ghost Composites for Hard-To-Transfect Cells
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for delivering exogenous materials to cells, such as therapeutics and imaging agents, face challenges including low cellular uptake, toxicity, and inefficiencies in transfection, particularly in Hard-To-Transfect cells, with liposomal systems being unstable and viral methods posing safety concerns.
Innovation Solution
Development of biomolecular composites comprising cell ghosts emptied of cytosolic contents, fused with lipids and vesicular structures, and optionally incorporating fusogenic lipids and peptides, to create micro or nano-sized vehicles for targeted delivery of cargo molecules to cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If liposomal formulations are used for delivery, then toxicity is reduced, but cellular uptake and stability remain insufficient
Solution Approach 1:
The invention uses cell ghosts as a composite material that combines the benefits of liposomes (low toxicity) with cellular membrane components (high stability and biocompatibility). The cell ghost structure provides both the safety profile needed for therapeutic delivery and the structural integrity required for colloidal and biological stability, resolving the contradiction between toxicity reduction and stability maintenance.
2Object-affected harmful factors
If liposomal systems are used, then toxicity is reduced, but cellular uptake by target cells is low
Solution Approach 1:
The cell ghost delivery system incorporates specific cellular membrane components and surface markers that provide local quality enhancements for target cell recognition and uptake. The membrane proteins and surface characteristics of the cell ghost are specifically adapted to interact with target cells, thereby improving cellular uptake while maintaining the low toxicity profile of liposomal systems.
3Object-affected harmful factors
If current non-viral transfection methods are used, then safety is improved, but transfection rates are low or cell toxicity is high
Solution Approach 1:
The invention changes the physical and chemical parameters of the delivery system by using cell ghosts with optimized size (less than 6 μm hydrodynamic diameter) and membrane composition. These parameter changes enable the system to achieve high transfection rates in Hard-To-Transfect cells while maintaining low cell toxicity, overcoming the limitations of current non-viral methods.
4Productivity
If viral transfection methods are used, then transfection efficiency is improved, but safety concerns arise
Solution Approach 1:
The invention creates a non-viral copy of viral delivery mechanisms by using cell ghosts that mimic the cellular recognition and uptake processes of viral vectors. This copying approach achieves high transfection efficiency similar to viral methods while eliminating the safety concerns associated with viral contamination, immunogenicity, and insertional mutagenesis.
5Productivity
If cell size is reduced to less than 6 μm, then delivery efficiency is improved, but manufacturing complexity increases
Solution Approach 1:
The invention performs preliminary actions during cell ghost preparation by pre-emptively removing cytosolic contents and pre-forming the membrane structure before loading with therapeutic cargo. This preliminary preparation simplifies the overall manufacturing process by creating a stable, pre-configured delivery vehicle that is ready for straightforward cargo loading, thereby reducing overall manufacturing complexity despite the size reduction requirement.
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
Enhances cellular uptake and transfection efficiency, reducing toxicity and improving delivery of therapeutic and imaging agents to target cells, including Hard-To-Transfect cells, while maintaining stability and safety.
Implementation Method 1
removing all or substantially all of the cytosolic contents of the cell including the nucleus and nuclear contents by exposing the cell to an osmotically active solution that is hypotonic to the cell
Implementation Method 2
fused with lipids and vesicular structures, and optionally incorporating fusogenic lipids and peptides
Data Source
AI summary
The present invention provides a biomolecular composite which is a ghost cell which has been emptied of all or substantially all of the cytosolic contents of the cell including the nucleus and nuclear contents, preferably further having been fused with exogenous amphipathic molecules, wherein said composite has a hydrodynamic diameter of less than 6 μm. The biomolecular composite may contain a cargo molecule and be capable of targeting a cell or tissue. Also provided are methods of preparing ghost cells, methods of preparing biomolecular composites and methods for their use.