Chemotherapeutic Drug-conjugated Microbeads Demonstrate Preferential Binding to Methylated Plasmid DNA.

Chemotherapeutic Drug-conjugated Microbeads Demonstrate Preferential Binding to Methylated Plasmid DNA.
Biotechnol J. 2018 Apr 10;:e1700701
Authors: Lin KN, Grandhi TSP, Goklany S, Rege K
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. We previously described the synthesis, characterization and evaluation of aminoglycoside-derived hydrogel microbeads ("Amikabeads") for pDNA binding. Here, we describe the generation and evaluation of novel chemotherapeutic drug-conjugated microbeads for application in pDNA binding and recovery. Chemotherapeutic drug-conjugated Amikabeads demonstrated higher binding of methylated pDNA compared to unmethylated pDNA in presence of high salt concentrations. Desorption of plasmids from drug-conjugated microbeads was facilitated by the use of organic modifiers. The observed differences in binding methylated vs. unmethylated DNA could make drug-conjugated microbeads useful in diagnostic applications. Our 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.
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Source: Biotechnology Journal - April 10, 2018 Category: Biotechnology Authors: Lin KN, Grandhi TSP, Goklany S, Rege K Tags: Biotechnol J Source Type: research