Polymerized Nucleotide Drugs

We are developing a platform for targeted and sustained delivery of anti-metabolic nucleotide analogs for chemotherapy. In addition to the well-known method of conjugating chemotherapeutic drugs to biopolymers and synthetic polymers, our lab also works on polymerization of nucleotide analogs using enzymatic routes. We exploit different DNA polymerases and molecular biology tools to generate oligomers of nucleotide drugs. Using DNA and RNA aptamers sequences, targeting ability can be bestowed to the polymerized nucleotides. It also explores aspects of biomolecular engineering and various bioconjugation methods to confer nuclease resistance to the nucleotide oligomers.



Deshpande, S.;  Yang, Y.;  Chilkoti, A.; Zauscher, S., Chapter Six - Enzymatic synthesis and modification of high molecular weight DNA using terminal deoxynucleotidyl transferase. In Methods in Enzymology, Bruns, N.; Loos, K., Eds. Academic Press: 2019; Vol. 627, pp 163-188.

Tang, L., Tjong, V., Li, N., Yingling, Y.G., Chilkoti, A. and Zauscher, S. (2014), Enzymatic Polymerization of High Molecular Weight DNA Amphiphiles That Self‐Assemble into Star‐Like Micelles. Adv. Mater., 26: 3050-3054.


PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response. I. Ozer; G.A. Pitoc; J.M. Layzer; A. Moreno; L.B. Olson; K.D. Layzer; A.M. Hucknall; B.A. Sullenger; A. Chilkoti. (2022).
Amphiphilic polynucleotides. A. Chilkoti; S. Zauscher; L. Tang; S. Deshpande. (2022).
Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity. L.B. Olson; N.I. Hunter; R.E. Rempel; H. Yu; D.M. Spencer; C.Z. Sullenger; W.S. Greene; A.K. Varanko; S.A. Eghtesadi; A. Chilkoti; D.S. Pisetsky; J.I. Everitt; B.A. Sullenger. (2022).