# Next generation of delivery platform for Prime editors based on an RNA vector for Sickle cell disease: the “all-in-one” vector

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2024 · $217,890

## Abstract

Abstract.
The choice of a delivery system for genetic manipulation or gene expression remains a topic of debate in the
research community. The development of a safe, unique, and efficient delivery vehicle that could promote gene
editing would significantly contribute to the field of gene therapy and regenerative medicine. Recently, we have
demonstrated that the Measles virus can be developed as a single cycle vector for multiple gene delivery. We
have shown that we can express the four reprogramming factors from on single measles genome and reprogram
adult human fibroblasts into induced pluripotent stem cells. We further have evidence that MeV can express the
gene-editing system CRISPR-Cas9 and lead to the correction of cells in the presence of a molecule of DNA
template. The goal of this application is to develop new prototype measles vectors that can either genetically
modify or correct a specific gene locus without relying on a DNA molecule using Prime Editors. As a proof of
concept, we will develop prototype vectors based on the vaccine strain of the measles virus, a negative-strand
RNA virus. The objectives of this application are (1) to establish the proof of principle that the MeV vector can
express the Prime Editing system (MeV-PE2). To do this, we will express the two elements required for prime
Editing: the Prime editor (PE2) and prime editor guide RNA (pegRNA), and test their functionality in producing
modified cells for the correction of Sickle cell disease (SCD) (2) In the second aim, we will introduce the latest
generation of Prime editor in MeV vector (MeV-PEmax), which consists of the PE2 and the introduction of (i) a
standard gRNA targeting the non-edited template, (ii) the MLH1dn protein to reduce mismatch repair or (iii) a
modified pegRNA to increase its stability. The proposed work is innovative, challenging, and significant, and if
successful, it will lead to the production of novel prototypes of “all-in-one” non-integrating RNA viral vectors for
cellular gene editing without the addition of an exogenous molecule of DNA. This work will open the future
development of safe vectors for gene editing and the production of corrected cells for multiple genetic disorders.
This new platform will have a significant impact in the field of gene therapy and regenerative medicine.

## Key facts

- **NIH application ID:** 10808443
- **Project number:** 1R21EB034346-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Patricia DEVAUX
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $217,890
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808443

## Citation

> US National Institutes of Health, RePORTER application 10808443, Next generation of delivery platform for Prime editors based on an RNA vector for Sickle cell disease: the “all-in-one” vector (1R21EB034346-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10808443. Licensed CC0.

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