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Updated: Sep 28, 2025

Practical Aspects of Sample Preparation and Setup of 1H R1ρ Relaxation Dispersion Experiments of RNA

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A split prime editor with untethered reverse transcriptase and circular RNA template.

Bin Liu¹, Xiaolong Dong¹, Haoyang Cheng¹

¹RNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.

Nature Biotechnology

|April 5, 2022

Summary

This summary is machine-generated.

Researchers developed a novel split prime editor (sPE) system to overcome the delivery challenges of large prime editors (PEs). This modular sPE system simplifies genome editing by reducing construct size and improving delivery efficiency.

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Area of Science:

Molecular Biology
Gene Editing Technologies
Biotechnology

Background:

Prime editors (PEs) are powerful gene editing tools but are limited by their large size and complex delivery.
Existing split genome editing systems often require complex engineering to link functional domains.

Purpose of the Study:

To develop a simplified and more efficiently deliverable split prime editor (sPE) system.
To assess the efficacy and safety of the novel sPE system in various mouse models.

Main Methods:

Engineered a split prime editor (sPE) where the Cas9 nickase (nCas9) is untethered from the reverse transcriptase (RT).
Delivered the sPE system using hydrodynamic injection and adeno-associated virus (AAV) vectors in mouse models.
Evaluated sPE efficiency in precise editing, insertion-deletion (indel) byproduct formation, tumor induction, and disease correction.

Main Results:

The sPE demonstrated comparable precise editing efficiencies to the parental PE3 without increased indel byproducts.
sPE delivery via hydrodynamic injection effectively modified β-catenin in mouse liver, driving tumor formation.
AAV-mediated delivery of sPE successfully corrected a disease-causing mutation in a mouse model of type I tyrosinemia.

Conclusions:

The developed modular split prime editor system simplifies PE delivery and optimization.
This novel sPE system, lacking inteins and affinity modules, offers a more flexible and potentially more efficient approach to prime editing.
The sPE system shows promise for in vivo gene correction and therapeutic applications.