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Chemotherapeutic Drug‐Conjugated Microbeads Demonstrate Preferential Binding to Methylated Plasmid DNA
Author(s) -
Lin Kevin N.,
Grandhi Taraka Sai Pavan,
Goklany Sheba,
Rege Kaushal
Publication year - 2018
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201700701
Subject(s) - biomanufacturing , plasmid , dna , conjugated system , chemistry , drug delivery , microbiology and biotechnology , biology , biochemistry , genetics , organic chemistry , polymer
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.