CRISPR base editing technology can correct Hurler syndrome before birth

Recent popular reports from Yimaike ★ Invitation to the grand event2021 Oncolytic Virus Drug Development Forum is about to open in Shanghai ★ The financing has reached hundreds of millions in half a year, and the oncolytic virus has entered the fast laneYimai New Observation Click on the picture and register now July 17, 2021 /MedClub News/--Hurler syndrome is a rare lysosomal storage disease that can cause organ swelling, muscle abnormalities, heart disease and a series of other problems
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Can cause the death of children
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It is caused by a single gene mutation-which makes it the prime target of gene editing therapy
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According to a report published in the journal Nature Communications by researchers from the University of Pennsylvania, they have now shown that in a mouse model, it is possible to use the gene editing system CRISPR to correct Hurler syndrome in mice before birth.

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In one study, they used an adeno-associated virus serotype 9 (AAV9) vector to provide an editor for a prenatal mouse model of Hurler syndrome, thereby correcting mutations in liver and heart cells
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The mutation that causes Hurler syndrome is called a DNA "base" mutation because the gene has adenine nucleotides instead of normal guanine nucleotides
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To correct it, researchers at the University of Pennsylvania used CRISPR base editing, a technique that only needs to destroy a single strand of DNA to convert adenine to guanine
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This single-strand editing method is considered safer than other CRISPR technologies that may cause off-target effects
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Researchers report that correcting the cells in the liver and heart of mice before birth produces a positive chain reaction that can improve the bones, metabolism and heart function of the mice, and increase the survival rate of untreated animals
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Penn's team also tested the gene editor on 10-week-old mice with Hurler syndrome and observed similar positive effects
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These mice did develop heart disease when they were four months old, similar to control mice, but CRISPR treatment seemed to slow the progression of heart decline
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The researchers reported that all prenatal and postnatal treatment mice survived to the end of the study, while some control mice died
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Recommended reading: Gene editing has made new progress in the treatment of fatal genetic diseases, and base editing strategies have become the future trend.
Yimai's new observation base editing has aroused the enthusiasm of biotechnology researchers and investors
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For example, last month, Beam Therapeutic and Apellis Pharmaceuticals reached a $75 million agreement to use the former's base editing technology to treat diseases caused by an overactive immune response
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▲ Principle of Beam’s gene editing technology platform (picture source: Beam’s official website) A few days before the transaction was concluded, Intellia’s first human experimental data showed that this gene editing therapy can significantly reduce transthyretin amyloidosis (ATTR) ) The patient’s transthyroxine levels.
This report caused the company’s stock price to soar
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It is worth mentioning that this is the first therapy to use in vivo gene editing technology for human trials.
According to data released by Intellia, NTLA-2001 in this clinical study showed a positive effect, which can be effectively reduced by a one-time injection.
The level of transthyretin (TTR) in the serum, TTR decreased by an average of 87%
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The decrease in serum TTR level is a known biomarker of ATTR amyloidosis, indicating that the patient is benefiting
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The gradual accumulation of TTR in tissues may cause neurological diseases and heart diseases
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This latest clinical data also shows the potential efficacy of gene editing technology in the treatment of other genetic diseases
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The new study at the University of Pennsylvania was led by William Peranteau, MD, a pediatric and fetal surgeon at the Children's Hospital of Philadelphia
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Two years ago, Peranteau's team used CRISPR to inactivate gene mutations in a mouse model of lung disease Surfactant Protein C (SFTPC) deficiency
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They also showed in the study that mice can be gene-edited before birth
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Last year, scientists at the Hubrecht Institute in the Netherlands used base editing technology to study a lung disease called "cystic fibrosis
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In this study, the researchers used mini-intestines or intestinal organoids to prove that base editing can correct the disease-causing CFTR mutations
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Peranteau pointed out that although currently known research results indicate that base editing may be a promising method for the treatment of Hurler syndrome, more preclinical studies are still needed to determine the safety of base editing to mothers and fetuses
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He said in a statement: "In view of the prenatal onset of the disease, the potential for non-invasive prenatal diagnosis, and the progressive and pathological nature of the disease, Hurler syndrome and other lysosomal storage diseases can be treated before birth.
Attractive target
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"Summary base editing is one of the latest advances in the field of genome editing.
It introduces single nucleotide variants (SNVs) into the DNA or RNA of living cells, which has great potential in the treatment of many genetic diseases
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Especially DNA and RNA bases.
The latest advances in specificity, efficiency, precision, and delivery of the base editor reveal that these technologies may bring exciting therapeutic opportunities
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With the continuous development of base gene editing technology, we look forward to this extremely Potential innovative technology can provide better treatment methods for the majority of patients, or provide a wider range of ideas for the development of more treatment strategies
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Reference materials: 1.
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