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Synthetic DNA delivery systems

Abstract

The ability to safely and efficiently transfer foreign DNA into cells is a fundamental goal in biotechnology. Toward this end, rapid advances have recently been made in our understanding of mechanisms for DNA stability and transport within cells. Current synthetic DNA delivery systems are versatile and safe, but substantially less efficient than viruses. Indeed, most current systems address only one of the obstacles to DNA delivery by enhancing DNA uptake. In fact, the effectiveness of gene expression is also dependent on several additional factors, including the release of intracellular DNA, stability of DNA in the cytoplasm, unpackaging of the DNA–vector complex, and the targeting of DNA to the nucleus. Delivery systems of the future must fully accommodate all these processes to effectively shepherd DNA across the plasma membrane, through the hostile intracellular environment, and into the nucleus.

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Figure 1: Schematic drawing of DNA delivery pathways with three major barriers: low uptake across the plasma membrane, inadequate release of DNA molecules with limited stability, and lack of nuclear targeting.
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Acknowledgements

Our work on DNA delivery systems is supported by the National Institutes of Health. We thank Phil L. Felgner for his helpful comments on historical activity in the development of synthetic DNA delivery systems and for his suggestion of several references that added substantially to the manuscript. We thank Douglas A. Lauffenburger for helpful discussions and for providing a prepublication copy of reference72.

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Correspondence to W. Mark Saltzman.

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Luo, D., Saltzman, W. Synthetic DNA delivery systems. Nat Biotechnol 18, 33–37 (2000). https://doi.org/10.1038/71889

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