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Branched Amphiphilic Peptide Capsules: Agents for Gene Delivery and Immunomodulation
Author(s) -
Tomich John M.,
Sukthankar Pinakin R.,
Barros Sheila de M.,
Withaker Susan K.,
WilkinsonNutsch Kayla M.,
Avila L. Adriana
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.785.11
Subject(s) - transfection , gene delivery , nucleic acid , peptide , in vitro , dna , amphiphile , in vivo , chemistry , genetic enhancement , microbiology and biotechnology , biology , biochemistry , gene , genetics , organic chemistry , copolymer , polymer
Branched Amphiphilic Peptides Capsules (BAPCs™) are a novel class of nano‐carriers constituted from the spontaneous co‐assembly of two unique, engineered peptide sequences. We recently reported on a thermally induced variant of BAPC™ that demonstrates promise as a vehicle for gene delivery and transfection. These BAPCs™ display a uniform size of 20–30 nm; they are easy to synthesize, stable and produce minimal immunogenic and inflammatory responses, in contrast to those commonly observed with viral and cationic lipid based approaches for gene delivery. BAPCs™ act as cationic nucleation centers allowing nucleic to wrap around them in a nucleosome like fashion, generating peptide‐nucleic complexes with sizes ranging from 50 to 250 nm. In this study, we combine the pre‐constituted BAPCs™ with a plasmid DNA construct encoding the green fluorescent protein (eGFP) in order to generate DNA/peptide complexes. We utilize these complexes to successfully transfect mammalian cells in vitro , yielding higher transfections rates than the commercially available lipid based reagent Lipofectin®, with minimal cytotoxicity. We then test the transfection system for the in vivo delivery of a DNA vaccine, previously designed to activate immune responses capable of controlling tumors induced by type 16 human papilloma virus (HPV‐16). We successfully demonstrate the efficacy of the DNA/BAPCs™ complexes in the in vitro activation of murine dendritic cells, and the enhancement of the associated vaccine's anti‐tumor potency, without significant toxic effects in vaccinated mice. Together these results indicate that the interaction of double stranded DNA to the cationic BAPCs™ nanoparticles represents a promising new in vitro and in vivo non‐viral gene delivery system. Support or Funding Information Partial support for this project was provided by the Terry Johnson Cancer Center at Kansas State University, The Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD) at Kansas State University This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .