Moderna deploys "next generation in vivo gene editing therapy" program

At the end of 2020, the US FDA urgently approved Moderna and BioNTech/Pfizer two mRNA vaccines for the prevention of COVID-19 pneumonia

Today, the success of mRNA vaccines in the field of COVID-19 has greatly stimulated and promoted the development and expansion of mRNA technology

According to existing orders, it is expected that the mRNA vaccine will bring Moderna up to US$20 billion in revenue this year

A few days ago, Moderna's plan to enter the field of gene editing was finally finalized

Moderna said that the cooperation between the two parties is not just about knocking out genes, modifying bases or repairing gene mutations

The two parties did not disclose the specific details of the cooperation, but it is understood that Metagenomi has a large number of new gene editing nucleases, and Moderna has rich experience in the field of mRNA technology and delivery

On a certain basis, gene editing therapy is extended to the clinic

Gene editing technology represented by CRISPR has developed rapidly in recent years, and many excellent gene editing start-ups have emerged

In 2018, Metagenomi researchers at the University of California, Berkeley, Brian Thomas and Jillian Banfield founded Metagenomi

So far, they have discovered hundreds of potential nucleases

On June 26, 2021, the international top medical journal "New England Journal of Medicine" (NEJM) published the world premiere of Intellia's CRISPR-based in vivo gene therapy editor founded by Nobel laureate Jennifer Doudna (Jennifer Doudna).

In this study, a lipid nanoparticle (LNP) delivery vehicle was used to deliver the sgRNA mRNA sequence targeting the disease-causing gene TTR gene and the optimized spCas9 protein to the liver

The results of this clinical trial of CRISPR gene editing therapy in vivo have greatly expanded the application range of CRISPR gene editing therapy

Moderna president Stephen Hoge (Stephen Hoge) said that Moderna has been paying close attention to the field of gene editing and is thinking about how its mRNA technology can help provide "gene editing products" to different organizations

In fact, in addition to the current pipeline of multiple vaccine research and development, Moderna has also begun to do research related to gene therapy

On May 25, 2021, Moderna's rare disease research team published a preclinical study on the use of lipid nanoparticles (LNP) to deliver engineered mRNA to treat glycogen storage diseases in the journal Nature Communications

Preventive vaccine

Vaccines against infectious diseases are still Moderna's core business
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In addition to mRNA-1273, which is used to prevent COVID-19, two other mRNA vaccines against COVID-19 mutant strains are undergoing clinical trials
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Clinical trials of mRNA vaccines against cytomegalovirus, human metapneumovirus (HMPV) and parainfluenza virus 3 (hMPV/PIV3), Zika virus, respiratory syncytial virus (RSV) and H7N9 influenza virus have begun
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Preclinical research on mRNA vaccines against Epstein-Barr virus, influenza virus, HIV and Nipah virus is ongoing
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Systemic Cell Therapy 

The mRNA-3927 for the treatment of propionic acidemia has begun clinical trials, and the mRNA treatments for methylmalonic acidemia, phenylketonuria, and type 1a glycogen storage disease are all in the preclinical stage
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These four diseases are rare autosomal recessive inherited diseases
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The correct mRNA is systematically delivered to the cell to express the correct function of the protein, so as to achieve the purpose of treating diseases
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Regenerative therapy

The AZD8601 project is a local mRNA treatment project that encodes vascular endothelial growth factor (VEGF-A)
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It was developed by Moderna in cooperation with AstraZeneca for the treatment of heart failure patients undergoing cardiac bypass (CABG) surgery
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The second phase of clinical trials is currently underway
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Systemic secretion and cell surface therapy 

Such patients also require systemic delivery therapy
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Among them, mRNA-1944 for Chikungunya virus has made the fastest progress
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The first phase of clinical trials has ended
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After intravenous infusion, antibodies that neutralize Chikungunya virus can be produced for a long time
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The remaining 3 mRNA treatments encoding relaxin, PD-L1 and IL2 are still in the preclinical stage
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Cancer vaccine 

These two cancer vaccines were jointly developed with Merke and have entered clinical trials
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The two vaccines are individualized cancer vaccine mRNA-4157 and cancer vaccine mRNA-5671 for KRAS mutants
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The former enhances the effect of immune checkpoint inhibitors by stimulating T cell immune response
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It can be used in combination with immunoassay inhibitors to improve the effect of cancer treatment
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The latter encodes the main mutants of KRAS: G12D, G12V, G13D, G12C, and is used for targeted treatment of non-small cell lung cancer, colorectal cancer, and pancreatic cancer caused by KRAS mutations
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Intratumoral Cancer Immunology 

In the field of intratumoral tumor immunology, Moderna has 3 therapies under development
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It injects mRNA encoding pro-inflammatory cytokines into tumors to stimulate the inflammatory response, turning "cold tumors" into "hot tumors", thereby improving immune examination
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The therapeutic effect of some inhibitors

These three therapies are mRNA-2416 encoding OX40L.
The treatment of solid tumors and lymphoma is in clinical phase I, and the treatment of ovarian cancer is in clinical phase II; mRNA-2752 encoding OX40L + IL23 + IL36γ is used to treat solid tumors and lymphoma.
Tumor is currently in clinical phase I; MED1191 encodes IL-12, which is a drug for the treatment of solid tumors jointly developed with AstraZeneca, and is currently in clinical phase 1
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However, there is news that Moderna has decided to abandon mRNA-2416
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  (Source: Internet, reference only)