Packaging of DNA by shell crosslinked nanoparticles.

Abstract:

:We demonstrate compaction of DNA with nanoscale biomimetic constructs which are robust synthetic analogs of globular proteins. These constructs are approximately 15 nm in diameter, shell crosslinked knedel-like (SCKs) nanoparticles, which are prepared by covalent stabilization of amphiphilic di-block co-polymer micelles, self-assembled in an aqueous solution. This synthetic approach yields size-controlled nanoparticles of persistent shape and containing positively charged functional groups at and near the particle surface. Such properties allow SCKs to bind with DNA through electrostatic interactions and facilitate reduction of the DNA hydrodynamic diameter through reversible compaction. Compaction of DNA by SCKs was evident in dynamic light scattering experiments and was directly observed by in situ atomic force microscopy. Moreover, enzymatic digestion of the DNA plasmid (pBR322, 4361 bp) by Eco RI was inhibited at low SCK:DNA ratios and prevented when [le]60 DNA bp were bound per SCK. Digestion by Msp I in the presence of SCKs resulted in longer DNA fragments, indicating that not all enzyme cleavage sites were accessible within the DNA/SCK aggregates. These results have implications for the development of vehicles for successful gene therapy applications.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Thurmond KB 2nd,Remsen EE,Kowalewski T,Wooley KL

doi

10.1093/nar/27.14.2966

keywords:

subject

Has Abstract

pub_date

1999-07-15 00:00:00

pages

2966-71

issue

14

eissn

0305-1048

issn

1362-4962

pii

gkc448

journal_volume

27

pub_type

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