Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype

By Hao Yin, Wen Xue, Sidi Chen, R. Bogorad, Eric Benedetti, M. Grompe, V. Koteliansky, Phillip A. Sharp, T. Jacks, Daniel G. Anderson. Nature Biotechnology, 2014

943 citations recorded by the source corpus.

We demonstrate CRISPR-Cas9–mediated correction of a Fah mutation in hepatocytes in a mouse model of the human disease hereditary tyrosinemia. Delivery of components of the CRISPR-Cas9 system by hydrodynamic injection resulted in initial expression of the wild-type Fah protein in ∼1/250 liver cells. Expansion of Fah-positive hepatocytes rescued the body weight loss phenotype. Our study indicates that CRISPR-Cas9–mediated genome editing is possible in adult animals and has potential for correction of human genetic diseases.

Subfields: Aging, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/83863be61c174889ac0365f3b3cc9929e92f2312

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. Eric S. Lander
2. Phillip A. Sharp

In Genetics

1. Jennifer A. Doudna
2. Lei S. Qi
3. Haifeng Wang
4. Marie La Russa
5. P. Hsu
6. Feng Zhang
7. E. Charpentier
8. Eric S. Lander

In Molecular Biology

1. Jennifer A. Doudna
2. Feng Zhang
3. Lei S. Qi
4. Haifeng Wang
5. Marie La Russa
6. P. Hsu
7. Eric S. Lander
8. E. Charpentier

Citations in the corpus

• Mechanisms and Regulation of Alternative Pre-mRNA Splicing (2015, background): “A variety of therapeutic strategies, such as small molecules (40, 41) and antisense oligonucleotides (42–44), as well as genome editing using CRISPR/Cas9 (45, 46), show promise for future intervention to ameliorate the diseasing-causing effects of human mutations on patterns of alternative splicing.”
• Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018, methodology): “) in vitro [61–64], while hydrodynamic injection has been employed to deliver CRISPR cassettes to the liver in vivo [46, 60].”
• Development and Applications of CRISPR-Cas9 for Genome Engineering (2014, positive): “Recently, hydrodynamic delivery of plasmid DNA encoding Cas9 and sgRNA along with a repair template into the liver of an adult mouse model of tyrosinemia was shown to be able to correct the mutant Fah gene and rescue expression of the wild-type Fah protein in 1 out of 250 cells (Yin et al., 2014).”
• Target specificity of the CRISPR-Cas9 system (2014, positive): “With exogenous template oligos, specific sequences such as HA-tag or GFP could be inserted into genes to label proteins [19,20], or to correct mutations in disease genes in human and mouse [21–23].”