Brief intro:
- Author: Xing Wang, Renxia Zhang, Dong Yang, Guoling Li, Zhanqing Fan, Hongting Du, Zikang Wang, Yuanhua Liu, Jiajia Lin, Xiaoqing Wu, Linyu Shi, Hui Yang, Yingsi Zhou
- Journal: Advanced Science
- Doi: https://www.doi.org/10.1002/advs.202206813
- Publication Date: 2023 Apr 25
Products/Services used in the paper
Quotation shows PackGene:AAV9 Production and Delivery to DMDQ1392X Mice: AAVs were produced by PackGene Biotech, and applied iodixanol density gradient centrifugation for purification.
Research Field:RNA editing
AAV Serotype:AAV9
Animal or cell line strain:8-week-old male DMDQ1392X mice
Abstract
Catalytically inactive CRISPR-Cas13 (dCas13)-based base editors can achieve the conversion of adenine-to-inosine (A-to-I) or cytidine-to-uridine (C-to-U) at the RNA level, however, the large size of dCas13 protein limits its in vivo applications. Here, a compact and efficient RNA base editor (ceRBE) is reported with high in vivo editing efficiency. The larger dCas13 protein is replaced with a 199-amino acid EcCas6e protein, derived from the Class 1 CRISPR family involved in pre-crRNA processing, and conducted optimization for toxicity and editing efficiency. The ceRBE efficiently achieves both A-to-I and C-to-U base editing with low transcriptome off-target in HEK293T cells. The efficient repair of the DMD Q1392X mutation (68.3±10.1%) is also demonstrated in a humanized mouse model of Duchenne muscular dystrophy (DMD) after AAV delivery, achieving restoration of expression for gene products. The study supports that the compact and efficient ceRBE has great potential for treating genetic diseases.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
