July 2022 ERCC webinar by Setty Magaña

Setty Magaña from Ohio State gave the July 2022 ERCC webinar.

This blog originated as a press release from Nagoya University. Thanks to them for allowing us to repost it here.

Researchers at Nagoya University in Japan have developed a new chemical-only process that may represent an important breakthrough in creating customized mRNA vaccines for a variety of diseases and allow for the inexpensive preparation of mRNA in large quantities.

During the COVID-19 pandemic, mRNA vaccines were successfully used to boost immunity. These vaccines teach cells how to make a protein that triggers the body’s immune response, allowing its natural defenses to recognize the invading virus. However, current vaccines that use biological processes do not allow for the precise molecular design of mRNA, which limits their use in creating new vaccines as variants emerge.

As published in ACS Chemical Biology, a research group led by Professor Hiroshi Abe and Associate Professor Naoko Abe of the Graduate School of Science at Nagoya University has developed the first completely chemical synthesis method for mRNA.

In their study, the group synthesized a part of the mRNA called the cap. The cap is important because it promotes the translation of mRNA into proteins and protects mRNA from degradation. To prepare synthetic mRNA, such as that used in vaccines, the two currently used biological methods rely on enzymes to incorporate the cap structure into the mRNA. However, the researchers found that their technique could synthesize a variety of chemically modified mRNA strands with a cap structure.

According to Professor Abe, “our research suggests that it is possible to make mRNAs with precisely introduced chemical modifications with complete control over the process. The molecular design reported in our study exhibits five times higher translational activity than that of enzyme-produced natural-type mRNA. This means that mRNA can be synthesized in large quantities at low cost using chemical synthesis.”

Chemically modified mRNA could be used to create customized vaccines against a variety of infectious diseases including viruses and cancers. Professor Abe explains, “By introducing these chemical modifications, the mRNA becomes stable. This could allow for the creation of long-lasting and effective mRNA vaccines. In addition, it could allow mRNA to be administered directly instead of using lipid nanoparticles, which are used for delivery in current vaccines.”

“One of the exciting implications of this research is that this could be used in the next generation of vaccines,” the researchers said. “We hope that the capping method reported here will be of great use in the development of RNA therapeutics.”

The study, “Complete Chemical Synthesis of Minimal Messenger RNA by Efficient Chemical Capping Reaction,” was published in ACS Chemical Biology on May 24, 2022.

Authors:
Naoko Abe, Akihiro Imaeda, Masahito Inagaki, Zhenmin Li, Daisuke Kawaguchi, Kaoru Onda, Yuko Nakashima, Satoshi Uchida, Fumitaka Hashiya, Yasuaki Kimura, and Hiroshi Abe

The study was supported by the AMED LEAP project ‘Innovation of Chemistry-Based Molecular Design and Production Methods for mRNA and its Application to Vaccines’, which started in FY2021.

Reference

Abe N et al. Complete chemical synthesis of minimal messenger RNA by efficient chemical capping reaction. ACS Chem Biol AOP 2022-05-24. doi: 10.1021/acschembio.1c00996 PMID: 35608277.

This blog originated as a press release from the Johns Hopkins Kimmel Cancer Center. Thanks to them for allowing us to repost it here.

It may be possible to identify the presence of an aggressive brain tumor in children by studying their cerebrospinal fluid, according to new research led by Johns Hopkins Kimmel Cancer Center investigators.

Comparing cerebrospinal fluid samples from 40 patients with medulloblastoma — the most common malignant brain tumor in children, accounting for 10% to 15% of pediatric central nervous system tumors — and from 11 healthy children without the disease, investigators identified 110 genes, 10 types of RNA–the machinery that translates proteins–called circular RNAs, 14 lipids and several metabolites that were expressed differently between the two groups. While these details were not specific enough to distinguish among the four subtypes of medulloblastoma, they could be used to identify the presence of cancer versus normal fluid. A description of the work was published in the journal Acta Neuropathologica Communications.

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Extracellular vesicles (EVs) are small membrane-bound particles that are loaded with various proteins, RNA, DNA, and lipids, and secreted by cells. Interest in these vesicles has grown in recent years with mounting evidence that EVs act as intercellular communication systems, transferring their selected cargo to other cells to confer specific effects on target cell biology. However, the processes that direct specific RNAs and proteins into these specialized vesicles remain largely unknown. In the April 25th, 2022 edition of Developmental Cell, Alissa Weaver, M.D., Ph.D. and her research team at the Vanderbilt Center for Extracellular Vesicle Research have uncovered subcellular hubs of EV formation that selectively assemble RNA-containing EVs. These hubs are located at membrane contact sites (MCS) where the endoplasmic reticulum (ER) interacts with EV biogenesis membranes, including late endosomal multivesicular bodies (MVBs) (ER-MVB MCS). Shedding much needed mechanistic light, the group further pinpointed the ER MCS membrane tether protein VAP-A and its binding partner ceramide transfer protein (CERT) as key drivers in this process.

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