Combinatorics

Pathology

Tay-Sachs disease

Disease

Population

First generation

Mathematics

Biology

Prime (order theory)

Rabbit (cipher)

Computer science

Computer security

Medicine

Environmental health

Cell Discovery

Tay-Sachs disease (TSD) is a progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of β-hexosaminidase A (HexA) 1 .The four-bases (TATC) insertion in exon 11 of the HEXA (HEXA ins TATC) accounts for 80% of Tay-Sachs disease from the Ashkenazi Jewish population 2 .However, no typical clinical phenotypes, such as neurological abnormalities, the restricted pattern of distribution of GM2-ganglioside and membranous cytoplasmic bodies in the brain, were observed in HEXA -/-mouse models, due to the difference in the ganglioside degradation pathways in mice and human 3 .Thus, it is desired to generate an ideal animal model to accurately mimic HEXA ins TATC in TSD patients.CRISPR-Cas9 systemmediated HDR 4 has been used to generate the mutation of HEXA ins TATC, however, low efficiency and high indels impede its application.Recently Anzalone et al. 5 described a "search-andreplace" genome editing technology named prime editing (PE) that mediates 12 possible base-to-base conversions, without requiring DSBs or donor DNA templates in human cells.In addition, a previous study showed that, compared to mice, the late onset of TSD in adult rabbits 6 shared more similarities with human regarding physiology, anatomy, and genetics 7 .Thus, we generated a novel TSD rabbit model using the PE system, and characterized

Efficient and precise generation of Tay–Sachs disease model in rabbit by prime editing system