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Updated: Feb 13, 2026

Kinetic Screening of Nuclease Activity using Nucleic Acid Probes

Kinetic Screening of Nuclease Activity using Nucleic Acid Probes

Published on: November 1, 2019

Evolution of sequence-defined highly functionalized nucleic acid polymers.

Zhen Chen^1,2,3, Phillip A Lichtor^1,2,3, Adrian P Berliner^1,2,3

¹Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.

Nature Chemistry

|March 7, 2018

Summary

This summary is machine-generated.

Researchers developed a novel method to create highly functionalized nucleic acid polymers (HFNAPs) using DNA-templated synthesis. These HFNAPs can bind disease-related proteins like PCSK9, opening doors for new therapeutics and materials.

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Area of Science:

Synthetic polymer chemistry
Nucleic acid engineering
Biomolecular design

Background:

Traditional polymers are limited by biological synthesis constraints.
Developing synthetic polymers with diverse functionalities is crucial for new applications.
Novel chemical building blocks are needed to expand polymer capabilities.

Purpose of the Study:

To develop a system for evolving sequence-defined synthetic polymers beyond biological limitations.
To create highly functionalized nucleic acid polymers (HFNAPs) with diverse chemical side chains.
To discover HFNAPs capable of binding specific protein targets implicated in human diseases.

Main Methods:

Ligase-mediated DNA-templated polymerization.
In vitro selection and reverse translation cycles.
Evolution of HFNAPs targeting PCSK9 and interleukin-6.

Main Results:

Discovered HFNAPs that bind PCSK9 and interleukin-6.
Evolved a PCSK9-binding HFNAP with high affinity (3 nM K_D).
Demonstrated potent inhibition of PCSK9-LDLR interaction by the evolved HFNAP.
Identified structure-activity relationships, highlighting the importance of specific side chains.

Conclusions:

Expanded the chemical space for evolvable polymers.
Demonstrated the potential of HFNAPs as therapeutic agents and for materials science.
Established a versatile platform for designing functional nucleic acid-based polymers.