Lipid-based systems for the intracellular delivery of genetic drugs
1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada. nmaurer@interchange.ubc.ca
Abstract:
Currently available delivery systems for genetic drugs have limited utility for systemic applications. Cationic liposome/plasmid DNA or oligonucleotide complexes are rapidly cleared from circulation, and the highest levels of activity are observed in 'first pass' organs, such as the lungs, spleen and liver. Engineered viruses can generate an immune response, which compromises transfection resulting from subsequent injections and lack target specificity. A carrier, which can accumulate at sites of diseases such as infections, inflammations and tumours, has to be a small, neutral and highly serum-stable particle, which is not readily recognized by the fixed and free macrophages of the reticuloendothelial system (RES). This review summarizes lipid-based technologies for the delivery of nucleic acid-based drugs and introduces a new class of carrier systems, which solve, at least in part, the conflicting demands of circulation longevity and intracellular delivery. Plasmid DNA and oligonucleotides are entrapped into lipid particles that contain small amounts of a positively charged lipid and are stabilized by the presence of a polythylene glycol (PEG) coating. These carriers protect nucleic acid-based drugs from degradation by nucleases, are on average 70 nm in diameter, achieve long circulation lifetimes and are capable of transfecting cells.
Insights
New lipid-based carriers improve genetic drug delivery. These novel systems protect nucleic acids, enhance circulation time, and enable effective cell transfection for treating diseases like infections and tumors.
Area of Science:
- Biotechnology
- Nanotechnology
- Pharmacology
Background:
- Current genetic drug delivery systems face challenges with systemic application, including rapid clearance and immune responses.
- Cationic liposomes and engineered viruses have limitations in circulation stability, target specificity, and transfection efficiency.
- Effective carriers require properties like small size, neutral charge, serum stability, and RES evasion for disease site accumulation.
Purpose of the Study:
- To review lipid-based technologies for nucleic acid drug delivery.
- To introduce a novel carrier system addressing limitations of existing delivery methods.
- To achieve both prolonged circulation and efficient intracellular delivery of genetic drugs.
Main Methods:
- Entrapment of plasmid DNA and oligonucleotides into lipid particles.
- Incorporation of small amounts of positively charged lipids within the particles.
- Stabilization of lipid particles using polyethylene glycol (PEG) coating.
Main Results:
- The novel carriers protect nucleic acid drugs from nuclease degradation.
- Particles exhibit an average diameter of 70 nm.
- Achieved long circulation lifetimes and demonstrated capability for cell transfection.
Conclusions:
- The developed lipid-based carriers offer a promising solution for systemic genetic drug delivery.
- These carriers overcome limitations of rapid clearance and immune responses associated with previous systems.
- The technology facilitates targeted delivery and enhanced therapeutic efficacy for various diseases.
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