title: Providing Oligonucleotides with Steric Selectivity by Brush-Polymer-Assisted Compaction.
abstract: Difficult biopharmaceutical characteristics of oligonucleotides, such as poor enzymatic stability, rapid clearance by reticuloendothelial organs, immunostimulation, and coagulopathies, limit their application as therapeutics. Many of these side effects are initiated via sequence-specific or nonsequence-specific interactions with proteins. Herein, we report a novel form of brush-polymer/DNA conjugate that provides the DNA with nanoscale steric selectivity: Hybridization kinetics with complementary DNA remains nearly unaffected, but interactions with proteins are significantly retarded. The relative lengths of the brush side chain and the DNA strand are found to play a critical role in the degree of selectivity. Being able to evade protein adhesion also improves in vivo biodistribution, thus making these molecular nanostructures promising materials for oligonucleotide-based therapies.
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Xueguang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Thanh-Huyen
authors.initials: TH
authors.lastname: Tran
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Fei
authors.initials: F
authors.lastname: Jia
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Xuyu
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Sage
authors.initials: S
authors.lastname: Davis
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Swathi
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
authors.affiliation: Department of Chemistry and Chemical Biology and ‡Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D051379:Mice; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D009841:Oligonucleotides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; D011108:Polymers