Improving Poly(Amidoamine) Dendrimer Gene Delivery Via Physical Interaction with a Nuclear Localization Sequence Peptide
Statement of Purpose: The field of non-viral gene delivery has developed many sophisticated approaches in polymer and nanomaterial design to replicate the transfection efficiencies of their viral counterparts. Polycationic polymers are attractive options for delivering nucleic acids via their inherent electrostatic interactions, however, transfection rates remain relatively low. A possible cause is the highly efficient electrostatic attraction between cationic polymers and the negatively charged phosphate backbone of nucleic acids that aids in intracellular delivery also represents its transfection limitation; the interaction leads to poor dissociation of nucleic acids in the cytosol and hinders nuclear translocation and subsequent transfection. In this work, these limitations are addressed by using biocompatible concentrations of generation 4 (G4) poly(amidoamine) (PAMAM) dendrimers, and physically interacting a unique peptide containing a nuclear localization sequence (NLS) to promote translocation of the entire complex containing a genetic payload across the nuclear envelope. The results of this work indicate an improvement in transfection in vitro relative to gene delivery of G4 dendrimers without the use of the NLS peptide.
R. C. Cooper and H. Yang, "Improving Poly(Amidoamine) Dendrimer Gene Delivery Via Physical Interaction with a Nuclear Localization Sequence Peptide," Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium, vol. 40, pp. 574-574, Society for Biomaterials, Apr 2019.
42nd Society for Biomaterials Annual Meeting and Exposition 2019: The Pinnacle of Biomaterials Innovation and Excellence (2019: Apr. 3-6, Seattle, WA)
Chemical and Biochemical Engineering
Keywords and Phrases
Biocompatibility; Biomolecules; Electrostatics; Gene transfer; Genes; Nucleic acids; Peptides, Electrostatic attractions; Intracellular delivery; Non-viral gene delivery; Nuclear localization sequences; Nuclear translocations; Polyamidoamine dendrimers; Polycationic polymers; Transfection efficiency, Dendrimers
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International Standard Serial Number (ISSN)
Article - Conference proceedings
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06 Apr 2019