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A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells

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Engineering Considerations for Developing Next-Generation Oligonucleotide Therapeutics.

Sasha B Ebrahimi¹, Himanshu Bhattacharjee¹, Sujatha Sonti²

¹Emerging Drug Delivery Platforms, GlaxoSmithKline, 1250 S Collegeville Rd, Collegeville, PA, USA.

Nature Chemical Engineering

|June 2, 2025

Summary

This summary is machine-generated.

Chemical engineering is crucial for advancing oligonucleotide therapeutics beyond the liver. This involves biomolecular and process engineering to improve drug stability, targeting, and delivery for wider disease treatment.

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Area of Science:

Biotechnology
Chemical Engineering
Genetics

Background:

Oligonucleotide therapeutics offer a novel approach to treating diseases by targeting genetic material.
Current applications are limited due to challenges in delivering these drugs to tissues outside the liver.

Purpose of the Study:

To highlight the essential role of chemical engineering in overcoming delivery challenges for oligonucleotide therapeutics.
To discuss the integration of biomolecular and process engineering for next-generation therapeutics.

Main Methods:

Collaborative perspective from academic and industry experts.
Analysis of biomolecular engineering strategies for enhanced stability, targeting, and pharmacokinetics.
Discussion of process engineering techniques for oligonucleotide development.

Main Results:

Chemical engineering is pivotal for expanding the clinical utility of oligonucleotide therapeutics.
Interplay between biomolecular and process engineering is key to "undruggable" disease treatment.
Improved engineering enhances developability and clinical translation.

Conclusions:

Advancements in chemical and biomolecular engineering are necessary to broaden the application of oligonucleotide therapeutics.
Integrated engineering approaches will enable treatment of a wider range of diseases.
This perspective emphasizes the bench-to-bedside translation facilitated by engineering innovations.