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      The Progress and Promise of RNA Medicine—An Arsenal of Targeted Treatments

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          Abstract

          In the past decade, there has been a shift in research, clinical development, and commercial activity to exploit the many physiological roles of RNA for use in medicine. With the rapid success in the development of lipid–RNA nanoparticles for mRNA vaccines against COVID-19 and with several approved RNA-based drugs, RNA has catapulted to the forefront of drug research. With diverse functions beyond the role of mRNA in producing antigens or therapeutic proteins, many classes of RNA serve regulatory roles in cells and tissues. These RNAs have potential as new therapeutics, with RNA itself serving as either a drug or a target. Here, based on the CAS Content Collection, we provide a landscape view of the current state and outline trends in RNA research in medicine across time, geography, therapeutic pipelines, chemical modifications, and delivery mechanisms.

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            The biology, function, and biomedical applications of exosomes

            Raghu Kalluri, Valerie LeBleu (2020)
            The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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              Engineering precision nanoparticles for drug delivery

              Michael J. Mitchell, Margaret M. Billingsley, Rebecca M. Haley … (2020)
              In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Med Chem
                Journal ID (iso-abbrev): J Med Chem
                Journal ID (publisher-id): jm
                Journal ID (coden): jmcmar
                Title: Journal of Medicinal Chemistry
                Publisher: American Chemical Society
                ISSN (Print): 0022-2623
                ISSN (Electronic): 1520-4804
                Publication date (Electronic): 09 May 2022
                Electronic Location Identifier: acs.jmedchem.2c00024
                Affiliations
                [∥ ]CAS, a division of the American Chemical Society 2540 Olentangy River Road, Columbus, Ohio 43202, United States
                [‡ ]College of Veterinary Medicine, Kansas State University , Manhattan, Kansas 66506, United States
                [§ ]Nanotechnology Innovation Center Kansas State, Kansas State University , Manhattan, Kansas 66506, United States
                Author notes
                Author information
                https://orcid.org/0000-0002-1156-5184
                https://orcid.org/0000-0003-4698-6832
                https://orcid.org/0000-0003-2130-5818
                https://orcid.org/0000-0001-6711-369X
                Article
                DOI: 10.1021/acs.jmedchem.2c00024
                PMC ID: 9115888
                PubMed ID: 35533054
                SO-VID: 2541c5b5-8620-44c6-a708-96fde8eabfd5
                Copyright © © 2022 The Authors. Published by American Chemical Society
                License:

                This article is made available via the PMC Open Access Subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 06 January 2022
                Categories
                Subject: Perspective
                Custom metadata
                document-id-old-9 jm2c00024
                document-id-new-14 jm2c00024
                ccc-price

                ScienceOpen disciplines: Pharmaceutical chemistry
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                ScienceOpen disciplines: Pharmaceutical chemistry

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