The latest data of the new AAV9-mediated RNA targeting system is released, which can correct the molecular and functional defects of type 1 myotonic muscular dystrophy Yi Mai Meng broke the news

Recent popular reports from Yimaike ★Novo Nordisk's $3.
3 billion acquisition of Dicerna in a large-scale acquisition of Dicerna, the RNAi field re-emergesYimaiman broke the news ★Voyager announces preclinical data of vectorized HER2 antibody, positive for HER2-positive breast cancer brain metastasis dataYimaimeng Breaking the news November 27, 2021/eMedClub News/--Recently, Locanabio, Inc.
, a gene pharmaceutical company that develops treatments for patients with severe neuromuscular diseases, neurodegenerative diseases and retinal diseases, announced its forcefulness New preclinical data for the muscular dystrophy type 1 (DM1) project
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 Using its CORRECTx™ platform, in the muscle cells of DM1 patients and DM1 preclinical mouse models, Locanabio scientists demonstrated a dose-dependent reduction of toxic CUG lesions, which can lead to correction of selective RNA splicing, as well as myotonia or weakness The statistically significant reduction
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The data was published in the form of a poster at the Muscle Biology Society in 2021, with the poster titled "AAV9-mediated RNA targeting system corrects the molecular and functional defects of type 1 myotonic dystrophy"
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 "We are pleased with the continued progress of the DM1 project
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These data indicate that the Cas13d and PUF structures can lead to a significant reduction in nuclear toxic RNA foci through different mechanisms of action, as well as a significant reduction in RNA splicing and muscle rigidity
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" Locanabio Dr.
John Leonard, Chief Scientific Officer of the company said, “In addition, these data show that we have the ability to preferentially target toxic mutant alleles and retain the DMPK RNA produced by wild-type alleles.
This is a few notable features of our CORRECTx™ platform.
One of the characteristics
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We are deeply encouraged by these data and believe that they support the application of our CORRECTx™ platform in the treatment of DM1 and other repetitive expansion diseases
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”Unique RNA-targeted gene therapy Myotonic muscular dystrophy type 1 (DM1) is an autosomal dominant genetic disease that affects skeletal muscle, myocardium, gastrointestinal tract and central nervous system
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DM1 is caused by myotonic dystrophy Caused by mutations in the protein kinase (DMPK) gene
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This mutation leads to the repeat amplification of CTG trinucleotides
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The
amplified CTG is transcribed into toxic CUG repeats in DMPK RNA
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These toxic RNA repeats can cause disease symptoms.
Including progressive muscle atrophy, muscle weakness, and muscle rigidity (delayed relaxation of skeletal muscle), which is a sign of DM1
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It is estimated that 1 in 8000 people in the world suffers from myotonic muscular dystrophy.
40,000 people
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  ▲ DM1 disease development process (picture source: Locanabio official website) The modular RNA binding protein system developed by the CorRECTX™ platform can modify RNA through a variety of mechanisms, such as cutting, splicing, gene replacement, translation enhancement and editing
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These systems provide unique features, solve the limitations of other RNA targeting methods, and may provide new gene drugs for patients with neurodegenerative diseases, neuromuscular diseases and retinal diseases
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▲RNA binding protein system (Image source: Locanabio (Official website) Locanabio company loads Cas9 that has lost its catalytic activity onto AAV vectors and delivers it to the diseased area.
The mutant Cas9 protein can specifically bind to RNA to modify and edit RNA
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It is worth mentioning that, with its unique RNA binding protein system, the company has completed hundreds of millions of dollars in financing
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 In May 2019, Locanabio completed a US$55 million Series A financing led by ARCH Venture Partners.
The Series A funding will be used to support its modular RNA targeting-effector therapy for disease treatment
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The company pointed out that its approach is different from DNA targeted therapy and nucleic acid-based RNA targeting
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According to the chart on its website, the company will use gene therapy vectors to provide RNA-targeting proteins with RNA-modifying enzymes
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By targeting RNA, the company says its method avoids the risk of off-target effects in DNA and is suitable for solving many diseases related to RNA dysfunction
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 Recommended reading: New RNA-targeted protein therapy received US$55 million in financing, and RNA-modifying enzymes carried by gene therapy vectors avoid the risk of DNA off-target effects.
Series B financing, this financing will promote Locanabio's RNA-targeted gene therapy product portfolio and expand the technology platform to pursue a wide range of therapeutic indications
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RNA editing technology In recent years, many biotechnology companies have begun to pay attention to the field of RNA editing
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RNA editing can be divided into two main categories.
One is to use oligonucleotide sequences to recruit existing ADAR enzymes in human cells to modify mRNA sequences
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The other is to develop proteins that can bind to specific RNA sequences, and then "hang" effector proteins with different functions on these proteins
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 Locanabio is a typical second-type company.
In addition, the new generation of RNA single-base editor "REPAIR" developed by Zhang Feng's team belongs to this category.
The basic elements of "REPAIR" are the PspCas13b enzyme and ADAR2 protein
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Because the Cas13 protein only targets RNA, "REPAIR" can efficiently repair single nucleosides of RNA without changing DNA information and is safer.
It will provide a new tool for basic research and clinical treatment
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 Recommended reading: Science's new breakthrough: Zhang Feng's team has developed a new generation of RNA single-base editor! Will it be safer this time? Yimai Meng broke the news and the representative companies in the first category are mainly Shape Therapeutics, Korro Bio, ProQR Therapeutics and Vico Therapeutics
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 Shape's RNA editing technology is based on research published by Dr.
Prashant Mali in Nature Methods in February 2019
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Studies have shown that using only the modified guide RNA, it can be combined with the natural protease editor (ADAR) and guide it to the RNA sequence, thereby repairing disease-related RNA gene mutations
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After being launched in November 2019, Shape raised a huge amount of US$112 million in July this year, and reached a strategic cooperation with Roche in August, and is eligible for Roche’s total value of more than US$3 billion in advance and milestone payments
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  Recommended reading: Roche continues to increase gene therapy with US$3 billion, this time betting on RNA editingYimai Meng broke the news that Korro Bio’s platform is derived from the pioneering research of co-founder Dr.
Josh Rosenthal’s team.
The research team used a scale The guide RNA to ADAR (guide RNA to ADAR) RNA fragment allows the ADAR enzyme to edit the base at a specific position on the complementary RNA strand
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  Recommended reading: Is it easier to achieve clinical transformation than CRISPR? Another RNA base editing company came out.
Yimai Meng revealed that many disease information of humans is encoded in DNA, the "script of life
.
"
The emergence of gene editing technology has made it possible for scientists to modify DNA, bringing hope to cure diseases
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However, because genes carry the most fundamental information of life, editing DNA has safety and ethical concerns.
RNA editing provides another option to avoid permanent changes to the genome
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Reference materials: 1.
https:// -frontiers-in-myogenesis-conference-2021-301428572.
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https://c212.
net/c/link/?t=0&l=en&o=3365229-1&h=4033195142&u=http%3A%2F%2F com%2F&a=