Formulation of a peptide nucleic acid based nucleic acid delivery construct.

Bioconjugate Chemistry
Peter G MilliliMillicent O Sullivan

Abstract

Gene delivery biomaterials need to be designed to efficiently achieve nuclear delivery of plasmid DNA. Polycations have been used to package DNA and other nucleic acids within submicrometer-sized particles, offering protection from shear-induced or enzymatic degradation. However, cytotoxicity issues coupled with limited in vivo transfection efficiencies minimize the effectiveness of this approach. In an effort to improve upon existing technologies aimed at delivering nucleic acids, an alternative approach to DNA packaging was explored. Peptide nucleic acids (PNAs) were used to directly functionalize DNA with poly(ethylene glycol) (PEG) chains that provide a steric layer and inhibit multimolecular aggregation during complexation. DNA prePEGylation by this strategy was predicted to enable the formation of more homogeneous and efficiently packaged polyplexes. In this work, DNA-PNA-peptide-PEG (DP3) conjugates were synthesized and self-assembled with 25 kDa poly(ethylenimine) (PEI). Complexes with small standard deviations and average diameters ranging 30-50 nm were created, with minimal dependence of complex size on N/P ratio (PEI amines to DNA phosphates). Furthermore, PEI-DNA interactions were altered by the derivatization strat...Continue Reading

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Citations

Mar 17, 2012·Molecular Pharmaceutics·Meghan J ReillyMillicent O Sullivan
Mar 19, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alice GhidiniRoger Strömberg
Feb 18, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Kory M BlockerMillicent O Sullivan
Oct 16, 2015·Molecular Pharmaceutics·Nikki L Ross, Millicent O Sullivan
Sep 15, 2012·The Journal of Gene Medicine·John D LarsenMillicent O Sullivan
Jan 28, 2012·Molecular Pharmaceutics·Meghan J ReillyMillicent O Sullivan
Jan 5, 2020·Gene Therapy·Basil MathewKevin G Rice
Nov 2, 2019·Biochimica Et Biophysica Acta. Biomembranes·Mobashar Hussain Urf Turabe FazilRathi Saravanan

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