Chengzu Long, PhD

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Ph. D. , 2014 University of Texas Southwestern Medical Center

Chengzu Long Lab
Genome editing; CRISPR/Cas9; Cpf1; Neuromuscular Diseases; Duchenne muscular dystrophy; Dilated Cardiomyopathy

Contact Information

The Helen and Martin Kimmel Center for Stem Cell Biology
The Leon H. Charney Division of Cardiology
Department of Medicine
New York University School of Medicine
522 First Avenue, Smilow 701C
New York, NY 10016

Tel: (212)-263-9100
Fax: (212)-263-9115

Genome editing to model and treat cardiac and neuromuscular diseases

Monogenic disorders affect millions of people worldwide. The World Health Organization currently estimates that more than 10,000 diagnosed human diseases are known to be caused by an error in a single gene.  Although individually relatively rare, together these diseases affect approximately 1 in 100 individuals. The recent advance in novel precision genome editing technologies and human pluripotent stem cell biology are revolutionizing our approach to studying disease pathology and developing potential therapeutics. Our projects focus on advancing the novel genome editing technology to model and treat cardiac and neuromuscular diseases (Long et al., JAMA Neurology. 2016). Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing, we successfully prevented muscular dystrophy in a mouse model of Duchenne muscular dystrophy (DMD) (Long et al., Science. 2014; Long et al., Science. 2016). This paved the way for novel genome editing-based therapeutics in DMD. We have advanced genome editing to cells from DMD patients by engineering the permanent skipping of mutant exons in the genomes of DMD patient-derived induced pluripotent stem cells (iPSCs). We screened for optimal guide RNAs for Cas9 and Cpf1 capable of skipping of “hot spot” DMD mutant exons. To address several challenges for clinical applications of gene editing in humans and to test these human DMD guide RNAs in animal models, we are generating “humanized” mouse models of DMD by introducing the human exon mutations into the mouse Dmd locus. To optimize Myoediting and monitor the efficacy and progression of gene correction non-invasively in vivo, we also introduced reporter gene luciferase into these humanized mice. Genome editing with novel strains of humanized mice, as well as cardiomyocytes derived from patients cardiomyocytes (Zhang et al. Science Advances. 2017), has enabled us to optimize the correction of DMD mutations, providing a path toward a potential cure of the disease in patients. Our long-term goal is to adapt gene editing to postnatal cardiac and skeletal muscle cells and to leverage this approach to correct muscular dystrophy and other genetic diseases caused by mutations in humans.

Selected Publications: 

1. Zhang, Y. *, Long, C. *,†, Li, H., McAnally, JR., Baskin, KK., Shelton, JM., Bassel-Duby, R., Olson, EN†. (2017) CRISPR-Cpf1 correction of muscular dystrophy mutations in human cardiomyocytes and mice. Science Advances 3(4): e1602814 (*These authors contributed equally; †Corresponding author).

2. Long, C. *, Amoasii, L.*, Mireault, AA., McAnally, JR., Li, H., Sanchez-Ortiz, E., Bhattacharyya, S., Shelton, JM., Bassel-Duby, R., Olson, EN. (2016) Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science 351(6271):400-3 (*These authors contributed equally).

3. Long, C. *, McAnally, JR.*, Shelton, JM., Mireault, AA., Bassel-Duby, R., Olson, EN. (2014) Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA. Science 345(6201):1184-8 (* These authors contributed equally).

4. Long, C.*, Grueter, CE.*, Song, K.*, Qin, S., Qi, X., Kong, YM., Shelton, JM., Richardson, JA., Zhang, CL., Bassel-Duby, R., Olson, EN. (2014) Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor. Proceedings of the National Academy of Sciences USA 111(31):11521-6 (*These authors contributed equally).

5. Xu, M.*, Long, C. *, Chen, X., Huang, C., Chen, S., Zhu, B. (2010) Partitioning of histone H3-H4 tetramers during DNA replication-dependent chromatin assembly. Science 328(5974):94-8 (* These authors contributed equally).