June 22, 2024

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Moderna is pointing to the next generation of in vivo gene editing therapies

Moderna is pointing to the next generation of in vivo gene editing therapies


Moderna is pointing to the next generation of in vivo gene editing therapies.

mRNA giant Moderna officially enters the field of gene editing, pointing to the next generation of in vivo gene editing therapies.


At the end of 2020, the US FDA urgently approved two mRNA vaccines from Moderna and BioNTech / Pfizer for the prevention of COVID-19 pneumonia . In fact, long before the COVID-19 pandemic, mRNA vaccines have attracted a large number of pharmaceutical companies to participate in research and development with their unique advantages.

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


Based on existing orders, it is estimated that the mRNA vaccine will bring Moderna ‘s revenue up to US$20 billion this year . In the second quarter earnings conference call in August this year, Moderna CEO Stéphane Bancel stated that Moderna is interested in nucleic acid technology , gene therapy , gene editing , and new delivery technologies , and revealed its plans to enter the field of gene editing. .


A few days ago, Moderna’s plan to enter the field of gene editing has finally been settled. Moderna announced that it will cooperate with the gene editing startup Metagenomi to combine Metagenomi ’s CRISPR-based next-generation gene editing system and other gene editing systems with Moderna ’s mRNA LNP technology and delivery technologies, to develop the next generation of in vivo gene therapy editing process , the development of treatments for patients with severe genetic diseases.


Moderna said that the cooperation between the two parties is not just to knock out a gene, modify a base, or repair a gene mutation. The pursuit of this collaboration is greater, and it is to create new gene editing tools so that scientists can have better Gene editing tools are available, allowing doctors to better treat genetic diseases.


The two parties of this cooperation are not revealing the specific details of the cooperation, but it is known that Metagenomi has a large number of new gene editing nucleases, and Moderna has rich experience in the field of mRNA technology and delivery. The cooperation between the two parties is complementary to each other.

Promote gene editing therapy to the clinic on a certain basis. Moderna said that he hopes that in 5-10 years, when people consider in vivo gene editing, they will think of Moderna and Metagenomi at the same time.


The gene editing technology represented by CRISPR has developed rapidly in recent years, and many excellent gene editing startups have emerged. Why did Moderna choose Metagenomi , a startup that has only been established for more than 2 years ?

Moderna’s statement is that after seeing the data displayed by Metagenomi, people ” cannot refuse ” .


Metagenomi was founded in 2018 by Brian Thomas and Jillian Banfield , metagenomic researchers at the University of California, Berkeley. It completed the A+ round of financing in May of this year, with a total of $75 million in round A financing. The company uses machine learning to mine microbial genomes to find new nucleases that can be used for gene editing.

So far they have discovered hundreds of potential nucleases. According to founder Brian Thomas , the nucleases they have are superior to the existing CRISPR-Cas9 gene editing system in terms of gene editing efficiency, with editing efficiency exceeding 90%, and some even exceeding 95%.


Moderna is pointing to the next generation of in vivo gene editing therapies.


June 26, 2021, top international medical journal ” New England Journal of Medicine ” (NEJM) published a Nobel laureate Jennifer Dude Na (Jennifer Doudna) founded Intellia ‘s the world’s first clinical trial results CRISPR vivo gene therapy editor.


In this study, a lipid nanoparticle (LNP) delivery vector was used to deliver the mRNA sequence of the sgRNA targeting the disease-causing gene TTR gene and the optimized spCas9 protein to the liver. Successfully treated 6 patients with severe and rare genetic diseases with transthyretin amyloidosis (ATTR) .


The results of this clinical trial of CRISPR gene editing therapy in vivo have greatly expanded the application range of CRISPR gene editing therapy. It can be directly injected into the body for high-efficiency gene editing, which opens up a new way for the treatment of many genetic diseases. The new era of medicine.


Stephen Hoge , President of Moderna, said that Moderna has been paying close attention to the field of gene editing and is thinking about how its mRNA technology can help deliver “gene editing goods” to different organizations. He also said that now is a good time to expand in the direction of gene editing .



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


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 Nature Communications .


Moderna is pointing to the next generation of in vivo gene editing therapies.


Moderna R&D pipeline


Preventive vaccine


Moderna is pointing to the next generation of in vivo gene editing therapies.


Preventive vaccines for infectious diseases are the core business of Moderna . In addition to the mRNA-1273 for the prevention of COVID-19, two other mRNA vaccines against COVID-19 mutant strains are undergoing clinical trials.


Clinical trials for mRNA vaccines against cytomegalovirus , human metapneumovirus and parainfluenza virus 3 (hMPV/PIV3) , Zika virus , respiratory syncytial virus (RSV) , and H7N9 influenza virus have begun.

Preclinical research is under way for mRNA vaccines against Epstein-Barr virus , influenza virus , HIV , and Nipah virus .


Systemic intracellular therapy


Moderna is pointing to the next generation of in vivo gene editing therapies.


The mRNA-3927 for the treatment of propionic acidemia has started clinical trials, and mRNA therapies for the treatment of methylmalonic acidemia , phenylketonuria , and glycogen storage disease type 1a are all in the preclinical stage.


These four diseases are rare autosomal recessive inherited diseases. The correct mRNA is delivered systemically into the cell to express the correct function of the protein to achieve the treatment of the disease.


Local regenerative therapy


Moderna is pointing to the next generation of in vivo gene editing therapies.


The AZD8601 project is a local mRNA therapy encoding vascular endothelial growth factor (VEGF-A) . Developed by Moderna in cooperation with AstraZeneca , it is used to treat patients with heart failure who have undergone cardiac bypass graft (CABG) surgery. Phase 2 clinical trials are currently underway.


Systemic secretion and cell surface therapy



This category also requires systemic delivery therapy. Among them , mRNA-1944 for chikungunya virus has made the fastest progress. Phase 1 clinical trials have ended. After intravenous infusion, it can produce neutralizing chikungunya virus for a long time. Type antibody. The other three mRNA therapies encoding relaxin, PD-L1 and IL2 are still in the preclinical stage.


Cancer vaccine



These two cancer vaccines were jointly developed with Merke and have entered clinical trials. They are a personalized cancer vaccine mRNA-4157 and a cancer vaccine mRNA-5671 that targets KRAS mutants.

The former enhances the effect of immune checkpoint inhibitors by stimulating T cell immune response. It can be used in combination with immunoassay inhibitors to improve the effect of cancer treatment.

The latter encodes the main mutants of KRAS: G12D, G12V, G13D, and G12C, which are used for targeted treatment of non-small cell lung cancer, colorectal cancer, and pancreatic cancer caused by KRAS mutations.


Intratumoral Cancer Immunology



In the field of intratumoral cancer immunology, Moderna has 3 treatments under development. It injects mRNA encoding pro-inflammatory cytokines into tumors to stimulate an inflammatory response and turn “cold tumors” into “hot tumors” , thereby improving immune inspections. 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 1, and the treatment of ovarian cancer is in clinical phase 2. MRNA-2752, which encodes OX40L + IL23 + IL36γ , is used to treat solid tumors and lymphomas, and is in clinical phase 1. And MED1191, which encodes IL-12 , is jointly developed with AstraZeneca to treat solid tumors and is in clinical phase 1. However, there is news that Moderna has decided to abandon mRNA-2416.




Moderna is pointing to the next generation of in vivo gene editing therapies

(source:internet, reference only)

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