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Updated: May 26, 2026

DNA-Tethered RNA Polymerase for Programmable In vitro Transcription and Molecular Computation

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Published on: December 29, 2021

Sequence-Defined Digital Bottlebrush Polymers for Programmable Oligonucleotide Delivery.

Jiachen Lin¹, Tingyu Sun¹, Yun Wei¹

¹Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, 02115, USA.

Biorxiv : the Preprint Server for Biology

|May 25, 2026

Summary

This summary is machine-generated.

New "digital" bottlebrush polymers precisely control therapeutic delivery. These engineered polymers overcome limitations of conventional approaches, enabling targeted delivery to tissues like muscle and skin for improved oligonucleotide therapeutics.

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Area of Science:

Polymer chemistry
Biotechnology
Drug delivery

Background:

Oligonucleotide therapeutics show promise but face delivery challenges like rapid clearance and poor organ targeting.
Conventional bottlebrush polymers offer limited control over biodistribution due to uniform backbones.

Purpose of the Study:

To develop sequence-defined "digital" bottlebrush polymers for precise control over therapeutic delivery.
To engineer polymers with tailored chemical motifs for modified physiochemical properties and organ-biased biodistribution.

Main Methods:

Synthesized a library of sequence-defined "digital" bottlebrush polymers with controlled placement of lipids, cholesterol, and cationic groups on a polyphosphodiester backbone.
Systematically evaluated structure-property relationships within the polymer library.
Assessed polymer performance in a mouse model of rheumatoid arthritis using an antisense oligonucleotide targeting TNF-α.

Main Results:

Established distinct structure-property relationships for the digital bottlebrush polymers.
Achieved organ-biased systemic delivery to challenging tissues, including muscle and skin.
Demonstrated potent TNF-α knockdown and full functional recovery in a rheumatoid arthritis model with a single dose of spleen-homing polymer-conjugated oligonucleotide.

Conclusions:

Digital bottlebrush polymers provide a versatile platform for tailoring polymer properties and achieving targeted therapeutic delivery.
This design framework enables overcoming oligonucleotide delivery barriers for various therapeutic applications.