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 journalArticlepeer-review

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)
Article number1700701
JournalBiotechnology Journal
Volume13
Issue number11
DOIs
StatePublished - Nov 2018

Keywords

  • DNA technology
  • biotechnology
  • diagnostics
  • doxorubicin
  • epigenetics
  • hydrogels
  • hydrophobic interaction chromatography
  • plasmid DNA purification

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Molecular Medicine

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