Perfluorocarbon-Nucleic Acid Complexes for Safe Gene Delivery
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Solution Overview
Problem
Current non-viral gene transfer methods for nucleic acids are inefficient, toxic, and cause immune reactions, failing to achieve the efficiency of viral gene transfer while avoiding immune responses and cellular toxicity.
Innovation Solution
Development of perfluorocarbon (PFC) compounds linked with nucleic acids through predetermined breaking points, allowing for efficient cellular uptake and release of nucleic acids into the cytoplasm without accumulating in cells or causing immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If cationic polymers or lipids are used to transfer nucleic acids, then cellular uptake is improved, but toxicity increases
Solution Approach 1:
The invention changes the chemical parameters of the transport molecule by using perfluorinated compounds instead of traditional cationic polymers or lipids. The perfluorinated structure provides lipophilicity for membrane penetration without the toxic side effects of strong positive charges, thus improving transfection rate while reducing cellular toxicity
Solution Approach 2:
The invention creates a composite structure by covalently linking perfluorinated compounds with nucleic acids through predetermined breaking points. This composite molecule combines the lipophilic properties of perfluorinated compounds for efficient cellular uptake with the nucleic acid payload, while the predetermined breaking points allow for controlled release inside the cell, achieving high transfection rates with reduced toxicity
2Quantity of substance
If strongly positively charged molecules are used to increase loading rates of DNA or RNA, then transfection efficiency is improved, but cellular toxicity increases
Solution Approach 1:
The invention changes the charge parameter of the transport molecule from strongly positive (cationic) to neutral or weakly polar (perfluorinated). The perfluorinated compounds achieve nucleic acid loading through lipophilic interactions and covalent bonding rather than electrostatic attraction, maintaining high loading rates while eliminating the toxic effects of strong positive charges
3Productivity
If viral vectors are used for gene transfer, then transfection efficiency is improved, but immune reactions and safety issues occur
Solution Approach 1:
The invention uses perfluorinated compounds with predetermined breaking points as disposable transport vehicles. These compounds deliver the nucleic acid payload efficiently and then break down into harmless perfluorinated fragments and nucleic acids, avoiding the persistent immune reactions associated with viral vectors. The perfluorinated fragments are rapidly eliminated from the body without triggering immune responses
Solution Approach 2:
The perfluorinated compounds act as intermediary molecules that facilitate nucleic acid delivery without the immunogenic properties of viral vectors. They provide the necessary lipophilicity for cellular uptake and stable complex formation, then break down into non-toxic fragments, serving as a safe intermediary between the nucleic acid payload and the cellular target
4Productivity
If transport molecules remain in the cytoplasm after transport, then accumulation occurs, but cellular function is disrupted
Solution Approach 1:
The invention introduces dynamic behavior to the transport molecule through predetermined breaking points that are stable during transport but cleave under intracellular conditions. This allows the molecule to remain intact during cellular uptake for efficient transport, then dynamically break down inside the cell to release the payload and eliminate the transport vehicle, preventing accumulation and cellular disruption
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 PFC-nucleic acid complexes achieve higher cellular uptake and repeated use without immune responses, offering a safer and more effective alternative to viral gene transfer methods.
Implementation Method 1
The PFC-nucleic acid complexes achieve higher cellular uptake
Implementation Method 2
linked with nucleic acids through predetermined breaking points, allowing for efficient cellular uptake and release of nucleic acids into the cytoplasm
Data Source
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AI summary
The invention relates to a compound of general formula (I): A - B - C(F, G')- D - E - F - G - A' or a structure of general formula (II): A - B - C(F', G')- D - B - E - F - G - A' (II), wherein - A is at least one molecule selected from the group of the perfluorocarbons (PFCs), perfluorinated silicon compounds, and/or further perfluorinated compounds, - B is at least one predetermined breaking point in the form of a physically, chemically, or enzymatically severable bond, - C is absent or at least one linker molecule, - D is absent or at least one spacer molecule, - E is at least one molecule selected from the group containing nucleobases, nucleosides, nucleotides, oligonucleotides, nucleic acids, modified nucleobases, modified nucleosides, modified nucleotides, modified oligonucleotides, modified nucleic acids, monomers of peptide nucleic acids, oligomers of peptide nucleic acids, and peptide nucleic acids or other nucleic acid analogs, - F, F' is absent or at least one ligand, - G, G' is absent or at least one marker molecule, - A' is absent or has the meaning of A, and wherein the compounds i), ii), iii), iv), v), vi) are excluded. The invention further relates to the use of said compound for the non-viral transfer of molecule E into a cell, to a pharmaceutical composition containing said compound, and to the use of said pharmaceutical composition.