CRISPR gene editing used to cure a mouse of a liver disorder and is the first disease cured in a living animal using CRISPR

Using the new CRISPR gene-editing system based on bacterial proteins, MIT researchers have cured mice of a rare liver disorder caused by a single genetic mutation. the first evidence that this gene-editing technique, known as CRISPR, can reverse disease symptoms in living animals. CRISPR, which offers an easy way to snip out mutated DNA and replace it with the correct sequence, holds potential for treating many genetic disorders, according to the research team.

The recently developed CRISPR system relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this cellular system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.

At the same time, the researchers also deliver a DNA template strand. When the cell repairs the damage produced by Cas9, it copies from the template, introducing new genetic material into the genome. Scientists envision that this kind of genome editing could one day help treat diseases such as hemophilia, Huntington’s disease, and others that are caused by single mutations.

Scientists have developed other gene-editing systems based on DNA-slicing enzymes, also known as nucleases, but those complexes can be expensive and difficult to assemble.

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

Disease correction

For this study, the researchers designed three guide RNA strands that target different DNA sequences near the mutation that causes type I tyrosinemia, in a gene that codes for an enzyme called FAH. Patients with this disease, which affects about 1 in 100,000 people, cannot break down the amino acid tyrosine, which accumulates and can lead to liver failure. Current treatments include a low-protein diet and a drug called NTCB, which disrupts tyrosine production.

In experiments with adult mice carrying the mutated form of the FAH enzyme, the researchers delivered RNA guide strands along with the gene for Cas9 and a 199-nucleotide DNA template that includes the correct sequence of the mutated FAH gene.

Using this approach, the correct gene was inserted in about one of every 250 hepatocytes — the cells that make up most of the liver. Over the next 30 days, those healthy cells began to proliferate and replace diseased liver cells, eventually accounting for about one-third of all hepatocytes. This was enough to cure the disease, allowing the mice to survive after being taken off the NCTB drug.

“We can do a one-time treatment and totally reverse the condition,” says Hao Yin, a postdoc at the Koch Institute and one of the lead authors of the Nature Biotechnology paper.

“This work shows that CRISPR can be used successfully in adults, and also identifies several of the challenges that will need to be addressed moving forward to the development of human therapies,” says Charles Gersbach, an assistant professor of biomedical engineering at Duke University who was not part of the research team. “In particular, the authors note that the efficiency of gene editing will need to improve significantly to be relevant for most diseases and other delivery methods need to be explored to extend the approach to humans. Nevertheless, this work is an exciting first step to using modern gene-editing tools to correct the devastating genetic diseases for which there are currently no options for affected patients.”

To deliver the CRISPR components, the researchers employed a technique known as high-pressure injection, which uses a high-powered syringe to rapidly discharge the material into a vein. This approach delivers material successfully to liver cells, but Anderson envisions that better delivery approaches are possible. His lab is now working on methods that may be safer and more efficient, including targeted nanoparticles.

ABSTRACT

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 in 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.

15 pages of supplemental information

Related Nextbigfuture Article on Near Term Transhumanism

This relates my look at near term transhumanism, I see older Tiger Moms as being the driver of early adoption of genetic intelligence enhancement and the lifting of the One child policy in China.

China’s One child policy is being lifted just as embryo selection based upon intelligence for invitro fertilized (IVF) babies becomes possible and we are on the cusp of genetic engineering. Women in China who are now older were banned from having babies but now will be allowed to have children. Many will not be able to conceive naturally and will use IVF. I see IVF going from 400,000 per year worldwide to 2-8 million per year over the next 10 years. IVF babies are more easily embryo selected and accessible for genetic modification. This would provide an economic boost to China in 20-30 years and the beginnings of a significant societal shift.

* Older women use IVF more than younger women.
* Societal shifts that cause more older women to use IVF to have children means more opportunity for embryo selection and genetic intelligence enhancement.
* Countries that permit embyro selection and genetic intelligence enhancement provide the opportunity for IVF to be used for enhancement
* Medical tourism to permissive countries is another means for older women to use IVF in combination with embryo selection or genetic enhancement.

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