Pini Perera, Ph.D., is particularly interested in embryonic development and the effect of environmental exposures during pregnancy. In this context, she studies the consequences of toxic exposures on imprinted genes—these are normal monoallelic genes, meaning that only one of the two parents’ genes is activated—and RNA regulation processes. Read more:

Abstract and Scholarship Deadlines Extended for Small Regulatory RNAs: From Bench to Bedside

RNA-based therapeutics provide a powerful new battery of agents to both diagnose and treat disease. However, while thousands of small regulatory RNAs are known, relatively little is known about their roles and targets, limiting their clinical applications.

This meeting aims to address these deficiencies by highlighting the emerging roles of srRNAs in fundamental biological processes and disease pathology. We will accelerate the bench to bedside applications of these discoveries by assembling the best minds in the field to collaboratively explore these new roles in health and disease, and translate these insights into powerful new clinical tools. 

The remarkable speed of vaccine development to address the SARS-CoV-2 coronavirus pandemic has highlighted the unique potential of mRNA therapy. In March 2020, only 10 weeks after the identification of the SARS-CoV-2 sequence, a phase I clinical trial was initiated. In December 2020, two lipid nanoparticle (LNP)–mRNA formulations obtained Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). Meanwhile, mRNA-based vaccines are also being developed against an array of human diseases such as respiratory syncytial virus (RSV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), influenza, and even cancer. mRNA-based drugs have broad potential applications and hold promise as vehicles for cancer therapy, as rare disease treatment, and even as enabling tools for in vivo genome editing.

These breakthroughs are built upon several generations of research in both academia and industry. The discovery of mRNA molecules and their functions was initiated in the 1960s. Since then, significant advances have been made in many areas including elucidating mRNA endogenous roles, understanding mRNA immunogenicity, modifying mRNA chemistry and structure, and manufacturing mRNA molecules on a large scale. In 2001, mRNA-engineered dendritic cells were examined clinically as a cancer immunotherapy. Because nucleic acids such as mRNA must reach the cell cytoplasm to function and are fragile in physiological conditions, vehicles are needed to help deliver them in vivo. This effort has been ongoing for decades, with early work on the nanoencapsulation and delivery of nucleic acids dating back to the 1970s. This extensive work on many different nanoformulations and with different nucleic acid payloads laid a foundation for the rapid development of the COVID-19 mRNA vaccines today.

The impact of mRNA therapy has motivated a broad array of ongoing research efforts to further extend its utility. These include efforts on the following: (1) The chemistry of delivery materials. Many different classes of delivery materials are being studied including, polymers, proteins, lipids, and even inorganic materials. (2) The rational design of mRNA sequences. Ongoing work seeks to establish design criteria for optimizing mRNA chemistry, sequences, and structures. (3) The pharmacokinetics and pharmacodynamics (PK/PD) of mRNA formulations. Extensive efforts continue to determine mRNA formulation biodistribution, kinetics, and immunogenicity. (4) The manufacturing of mRNA formulations. The requirement for billions of human vaccine doses makes clear the need for scalability, and efforts are focused on the cost-effective manufacture of pure and stable mRNA formulations. (5) The delivery to new tissue targets. mRNA formulations are being developed for a range of different tissues, and different formulations, and methods of application seek to extend the list of different cell types that can be treated in a safe and effective manner. We believe that we are still at the beginning of understanding the utility of mRNA as a drug and that the coming years will see innovations and advances in all these areas that will significantly expand the scope of mRNA therapy.

In this special issue of Accounts of Chemical Research, leading research groups share their exciting findings and provide insights into topics related to mRNA therapeutics. Link to PDF

Yizhou Dong and Daniel G. Anderson, Accounts of Chemical Research 2022 55 (1), 1-1

Sarah Slavoff, Yale University

Monday, February 7, 2022

4:00 pm - 5:30 pm

Zoom (passcode: 0102)

Tuesday, February 8, 2022

1:00 pm - 2:30 pm

Helge Grosshans, Friedrich Miescher Institute

Tuesday, February 8, 2022

3:00 pm - 4:00 pm

Zoom (passcode: 770277)

RNA Collaborative Seminar, Host: University of Science and Technology of China, RNA Institute

Max Planck Institute of Molecular Plant Physiology

Friday, February 11, 2022

12:00 pm - 1:00 pm

1060 Biological Sciences Building (BSB) 

Johns Hopkins University

Monday, February 14, 2022

4:00 pm - 5:00 pm

BSRB, ABC Seminar rooms (hybrid)

Co-hosted by the Department of Biological Chemistry and the Program in Biophysics

Beth Rousseau David Turner lab

Tuesday, February 15, 2022

2:00 pm - 3:00 pm

Zoom (passcode: 824971)

Yale University

Wednesday, February 16, 2022

9:30 am - 10:30 am

Postdoctoral position in RNA Biology at The Eric Lai lab, NYC in small RNAs and alternative mRNA processing

The Lai lab at Sloan Kettering Institute, NYC has multiple postdoctoral positions available to join our efforts in RNA mechanisms and biology. Our group uses integrated approaches to study several areas in post-transcriptional regulation, but we have particular interests in alternative mRNA processing in the nervous system (e.g. global regulation of splicing and 3' UTR isoforms by ELAV/Hu RBPs) and small RNA biogenesis and function (not only for miRNAs, but also for the enigmatic endogenous RNAi pathway, which we recently found to suppress intragenomic conflict.) Our goals are to define new molecular mechanisms that govern the appropriate tissue-specific processing of mRNA isoforms, to elucidate these genomewide and reveal connections to allied regulatory pathways, and define their in vivo biology and phenotypes using precision genetics. More information on our lab's efforts here.

The ideal candidate will be able to combine their background in RNA biology with our extensive unpublished tools and resources, in Drosophila and mammalian systems. We welcome applicants with experience in molecular genetic methods and/or in computational genomics, and also open to candidate proposals for new areas of research that build on our directions. We have an interactive, multidisciplinary, and collaborative team engaged in diverse topics in regulatory biology, and the Sloan Kettering Institute provides a vibrant research community committed to inclusivity and diversity.

Positions are currently available and funded by a new 4-yr NIH-R01 grant, and include nearby subsidized housing and benefits. Please provide CV, motivation letter and references to Eric Lai, laie@mskcc.org.

Our members' publications are available through Altmetrics. Queries are currently available: CRISPR, microRNA, molecule, RNA, RNA therapeutics, transcriptome, and translation. Below are recent highlights.

Pseudouridine synthase 7 is an opportunistic enzyme that binds and modifies substrates with diverse sequences and structures, Meredith K. Purchal, Daniel E. Eyler, Mehmet Tardu, Monika K. Franco, Megan M. Korn, Taslima Khan, Ryan McNassor, Rachel Giles, Katherine Lev, Hari Sharma, Jeremy Monroe, Leena Mallik, Markos Koutmos and Kristin S. Koutmou, Proceedings of the National Academy of Sciences, 1/25/2022, DOI: 10.1073/pnas.2109708119

Pseudouridine is among the most-abundant RNA modifications. We present a framework for conceptualizing how eukaryotic pseudouridine synthases select their substrates. This work reveals the structure of yeast pseudouridine synthase 7 (Pus7) and presents cell-based and biochemical investigations of enzyme binding and activity. We demonstrate that Pus7 interacts promiscuously with RNAs containing UGUAR sequences. Our observations raise the question of why these enzymes only modify <5% of UGUAR sequences in the transcriptome, suggesting that factors beyond inherent enzyme properties—such as protein localization, local RNA structure, and RNA–protein interactions—principally shape Pus7 substrate selection. These findings support a role for Pus7 in providing cells with a mechanism to rapidly alter protein synthesis in response to cellular conditions.

To share your news and comments, please contact Martina Jerant