Fatty acid–spermine conjugates as DNA carriers for nonviral in vivo gene delivery
- 3 September 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Gene Therapy
- Vol. 16 (12), 1429-1440
- https://doi.org/10.1038/gt.2009.108
Abstract
The lack of efficient in vivo gene delivery is a well-known shortcoming of nonviral delivery vectors, in particular of chemical vectors. We developed a series of novel nonviral carriers for plasmid-based in vivo gene delivery. This new transport device is based on the assembly of DNA plasmids with synthetic derivatives of naturally occurring molecules—fatty acid–spermine conjugates (or lipospermines). We tested the ability of these fatty acid conjugates to interact with plasmid DNA (pDNA) and found that they formed DNA nanocomplexes, which are protected from DNase I degradation. This protection was shown to directly correlate with the length of the aliphatic component. However, this increase in the length of the hydrocarbon chain resulted in increased toxicity. The cationic lipids used for transfection typically have a C16 and C18 hydrocarbon chain. Interestingly, toxicity studies, together with further characterization studies, suggested that the two most suitable candidates for in vivo delivery are those with the shortest hydrocarbon chain, butanoyl- and decanoylspermine. Morphological characterization of DNA nanocomplexes resulting from these lipospermines showed the formation of a homogenous population, with the diameter ranging approximately from 40 to 200 nm. Butanoylspermine was found to be the most promising carrier from this series, resulting in a significantly increased gene expression, in relation to naked plasmid, in both tissues herein targeted (dermis and M. tibialis anterior). Thus, we established a correlation between the in vitro properties of the ensuing DNA nanocarriers and their efficient in vivo gene expression.Keywords
This publication has 45 references indexed in Scilit:
- Activation of transgene expression in skeletal muscle by focused ultrasoundBiochemical and Biophysical Research Communications, 2009
- Electroporation-based DNA transfer enhances gene expression and immune responses to DNA vaccines in cattleVaccine, 2008
- Simple Modifications of Branched PEI Lead to Highly Efficient siRNA Carriers with Low ToxicityBioconjugate Chemistry, 2008
- Biodegradable polymers as non-viral carriers for plasmid DNA deliveryJournal of Controlled Release, 2008
- DNA condensation by poly-l-lysine at the single molecule level: Role of DNA concentration and polymer lengthJournal of Controlled Release, 2008
- Electroporation for Drug and Gene Delivery in the Clinic: Doctors Go ElectricMethods in molecular biology (Clifton, N.J.), 2008
- Electric Pulse‐Mediated Gene Delivery to Various Animal TissuesAdvances in genetics, 2005
- Transfection of airway epithelium by stable PEGylated poly-l-lysine DNA nanoparticles in vivoMolecular Therapy, 2003
- Minimal toxicity of stabilized compacted DNA nanoparticles in the murine lungMolecular Therapy, 2003
- In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysisBiomaterials, 2003