Charting a Future for Sequencing RNA and Its Modifications A New Era for Biology and Medicine (2024) / Chapter Skim
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5 Driving Innovation to Study RNA Modifications
5 Driving Innovation to Study RNA Modifications
Pages 129-156
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The field of RNA biology needs accurate, reproducible, and universally available tools and technologies for sequencing RNA and its modifications; a vibrant space where industry and academic researchers both compete and collaborate in creating and refining those tools and technologies; an end market sufficient to attract companies and guide innovation; and substantial public and philanthropic funding to address major barriers to progress. Furthermore, innovation in tools and technologies and in the application of RNA science requires a strategy that maintains U.S.
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Academic laboratories and a small number of companies have been at the forefront of developing direct sequencing strategies. One of the biggest limitations that this effort 130 Prepublication Copy
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Academic laboratories are a major market for these companies, so expanding research on RNA modifications and encouraging technology development in academia is likely to spur continued technology improvements in industry as well. This includes not only direct RNA sequencing methods themselves, but also synthesis of oligonucleotides and other modified reference standards and development of computational analysis tools.
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Sponsored competitions may also be highly productive. For example, open competitions for the development of computational analysis methods for calling chemical modifications from direct RNA sequencing data could lead to novel machine learning 1 See https://www.sbir.gov/about (accessed November 6, 2023)
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. The report notes important priorities for RNA research, including "RNA chemistry," and goes on to recommend "a national mission for the whole RNA science and technology pipeline in Australia, driven by strategic investment and prioritization across funding schemes" (Australian Academy of Science and the Australia and New Zealand RNA Production Consortium.
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education to promote earlier engagement and exposure to RNA biology with the aim of promoting awareness of and interest in the topic. Students currently studying RNA biology commented that incorporating RNA biology into high school education could open students' eyes earlier to the impact of RNA and its modifications on society.5 Incorporating RNA biology into high school education could lead to a more informed population, which will be important as mRNA vaccines and other RNA-based diagnostics and therapeutics enter clinical and public health spaces (see "Public Outreach" below)
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Understanding in these areas is critical for analyzing the large datasets generated from mapping RNA modifications and sequencing modified RNA transcripts. A major part of studying RNA modifications depends on bioinformatic analysis pipelines to process highthroughput sequencing data and derive conclusions from these data.
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Chemists could advance the synthesis of novel phosphoramidites used in making standards for RNA modifications. Computer and data scientists are needed to develop algorithms and machine learning models to infer modification sites from RNA sequencing data.
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RNA science will continue to move forward if all the drivers of innovation are put into play. However, without changes that foster innovation and risk-taking in the development of direct sequencing technologies, the pace and robustness of innovation are in question, and the United States risks falling behind other countries that are making significant investments in RNA-related research and development.
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Although specific methodologies related to RNA modifications are lacking in some core facilities, third-generation sequencing technologies, such as those of Oxford Nanopore Technologies, are available. As methodologies for sequencing RNA modifications become available, core facilities that house the necessary instruments and staff expertise will become increasingly valuable.
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For example, direct sequencing via mass spectrometry typically requires far more RNA than is actually consumed or analyzed by the instrument itself. Of note here, whether used in global analysis of modified nucleosides or used in RNA modification mapping by the bottom-up technique (see Chapter 3)
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For example, the National Nanotechnology Initiative, research and development initiative on nanotechnology coordinated under the White House National Science and Technology Council, was envisioned with the promise of technological advances supporting 146 Prepublication Copy
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The Glycoscience Program included an SBIR/STTR component supported through multiple NIH institutes that aimed to develop commercially available, affordable tools and technologies for glycoscience. The BRAIN 2025 report (ACD BRAIN Initiative, 2014)
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2022. "A standards organization for open and FAIR 150 Prepublication Copy
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Santa Monica, CA: RAND Corporation. Prepublication Copy 153
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