Chemotherapeutic Drug-Conjugated Microbeads Demonstrate Preferential Binding to Methylated Plasmid DNA

Kevin N. Lin, Taraka Sai Pavan Grandhi, Sheba Goklany, Kaushal Rege

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Plasmid DNA (pDNA) is an attractive therapeutic biomolecule in several diseases including cancer, AIDS, cystic fibrosis, Parkinson's disease, and Alzheimer's disease. Increasing demand for plasmid DNA as a therapeutic biomolecule for transgene expression or vaccine applications necessitate novel approaches to bioprocessing. The synthesis, characterization and evaluation of aminoglycoside-derived hydrogel microbeads (Amikabeads) for pDNA binding is described previously. Here, the generation and evaluation of novel chemotherapeutic drug-conjugated microbeads for application in pDNA binding and recovery is described. Chemotherapeutic drug-conjugated Amikabeads demonstrate higher binding of methylated pDNA compared to unmethylated pDNA in presence of high salt concentrations. Desorption of plasmids from drug-conjugated microbeads is facilitated by the use of organic modifiers. The observed differences in binding methylated versus unmethylated DNA can make drug-conjugated microbeads useful in diagnostic as well as therapeutic applications. These results demonstrate that anti-cancer drugs represent a diverse set of ligands that may be exploited for molecular engineering of novel DNA binding materials for applications in delivery, diagnostics, and biomanufacturing.

Original languageEnglish (US)
JournalBiotechnology Journal
DOIs
StateAccepted/In press - Jan 1 2018

Keywords

  • Biotechnology
  • Diagnostics
  • DNA technology
  • Doxorubicin
  • Epigenetics
  • Hydrogels
  • Hydrophobic interaction chromatography
  • Plasmid DNA purification

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Molecular Medicine

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