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.

nucleotide

Publications

Deshpande, Sonal, Yunqi Yang, Stefan Zauscher, and Ashutosh Chilkoti. “Enzymatic Synthesis of Aptamer-Polynucleotide Nanoparticles with High Anticancer Drug Loading for Targeted Delivery.” Biomacromolecules 25, no. 1 (January 2024): 155–64. https://doi.org/10.1021/acs.biomac.3c00888.

Olson, Lyra B., Nicole I. Hunter, Rachel E. Rempel, Haixiang Yu, Diane M. Spencer, Cynthia Z. Sullenger, William S. Greene, et al. “Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity.” IScience 25, no. 12 (December 22, 2022): 105542. https://doi.org/10.1016/j.isci.2022.105542.

Ozer, Imran, George A. Pitoc, Juliana M. Layzer, Angelo Moreno, Lyra B. Olson, Kyle D. Layzer, Angus M. Hucknall, Bruce A. Sullenger, and Ashutosh Chilkoti. “PEG-Like Brush Polymer Conjugate of RNA Aptamer That Shows Reversible Anticoagulant Activity and Minimal Immune Response.” Adv Mater 34, no. 10 (March 2022): e2107852. https://doi.org/10.1002/adma.202107852.

Deshpande, Sonal, Yunqi Yang, Ashutosh Chilkoti, and Stefan Zauscher. “Enzymatic synthesis and modification of high molecular weight DNA using terminal deoxynucleotidyl transferase.,” 627:163–88, 2019. https://doi.org/10.1016/bs.mie.2019.07.044.

Ozer, Imran, and Ashutosh Chilkoti. “Site-Specific and Stoichiometric Stealth Polymer Conjugates of Therapeutic Peptides and Proteins.” Bioconjugate Chemistry 28, no. 3 (March 2017): 713–23. https://doi.org/10.1021/acs.bioconjchem.6b00652.

Tang, Lei, Vinalia Tjong, Nan Li, Yaroslava G. Yingling, Ashutosh Chilkoti, and Stefan Zauscher. “Enzymatic polymerization of high molecular weight DNA amphiphiles that self-assemble into star-like micelles.” Advanced Materials (Deerfield Beach, Fla.) 26, no. 19 (May 2014): 3050–54. https://doi.org/10.1002/adma.201306049.

Patents

A. Chilkoti, Zauscher, S. , Tang, L. , and Deshpande, S. , “Amphiphilic polynucleotides”, 2022.

Chilkoti, A., Zauscher, S., Tang, L., Deshpande, S., "Amphiphilic polynucleotides", US Patent 11965164B2, issued April 23, 2024

Chilkoti, A., Zauscher, S., Tang, L., and Deshpande, S., "Amphiphilic polynucleotides". US Patent 11965164B2, issued April 23, 2024. https://patents.google.com/patent/US11965164B2