Messenger RNA-Based Therapeutics and Vaccines: What’s beyond COVID-19?

With the rapid success in the development of mRNA vaccines against COVID-19 and with a number of mRNA-based drugs ahead in the pipelines, mRNA has catapulted to the forefront of drug research, demonstrating its substantial effectiveness against a broad range of diseases. As the recent global pandemic gradually fades, we cannot stop thinking about what the world has gained: the realization and validation of the power of mRNA in modern medicine. A significant amount of research has now been concentrated on developing mRNA drugs and vaccine platforms against infectious and immune diseases, cancer, and other debilitating diseases and has demonstrated encouraging results. Here, based on the CAS Content Collection, we provide a landscape view of the current state, outline trends in the research and development of mRNA therapeutics and vaccines, and highlight some notable patents focusing on mRNA therapeutics, vaccines, and delivery systems. Analysis of diseases disclosed in patents also reveals highly investigated diseases for treatments with these medicines. Finally, we provide information about mRNA therapeutics and vaccines in clinical trials. We hope this Review will be useful for understanding the current knowledge in the field of mRNA medicines and will assist in efforts to solve its remaining challenges and revolutionize the treatment of human diseases.

The annual number of global patents in the field of mRNA therapeutics increased steadily from 7 in 2000 to 180 in 2021 although the increase has been more significant for the past several years (Figure S1).Since 2000, fewer patents have been filed in this field.The At the end of 2019, probably catalyzed by the COVID pandemic, technology patents rose in the field of mRNA therapeutics worldwide, and the number of s each year increased significantly.

SI-2. Trend over time for patents related to mRNA vaccines
The global patent application in the field of mRNA vaccines showed a trend of slow rise at first and then rapid rise (Figure S2).From 2000 to 2019, the number of related patents in this field was relatively small, with the annual number of patent applications within 50.After 2020, the number of related patent applications in this field increased rapidly from 55 in 2020 to 175 in 2021, and the number of patents in 2022 is expected to be more than 160.As shown in Figure S3, the annual number of patents in the field of mRNA delivery systems generally shows a rising trend, although the increase was more significant over the past several years.From 2000 to 2002, the number of patent applications in this field was small.

SI-4. Trend over time for patents related to mRNA modification
From the annual trend, the number of global patent applications in the field of mRNA modification fluctuates, with a significant increase and peak in 2013, followed by a decline (Supplemental Figure S4).The trend of patent applications was relatively stable from 2015 to 2018, and after a brief decline in 2019, the number of patent applications showed a slow growth trend from 2020.

SI-5. Analysis of research topics in mRNA therapeutics patents
From the distribution of patent research topics as indicated by cluster analysis of CAS index terms, the global effort on mRNA therapeutics focused on drug development methodologies, disease indications, and mechanism of actions such as signallng molecules, immune responses, etc.(Supplemental Figure S5).key concepts for drug development include antitumor agents, pharmaceutical carriers, pharmaceutical nanoparticles, pharmaceutical liposomes, etc (red dots).In the studies of diseases and their mechanisms (green dots), key concepts for disease indications and machnistic studies includeimmunoglobulins and their heavy chains, single-chain antibodies, cell proliferation, etc. Key concepts for immune studies (blue dots) include terms such as antigens, T cells, cancer immunotherapeutics, and chimeric antigen receptors.The signaling molecules (yellow dots) that have been highly explored include CD28 antigen, CD3 antigen, CD8 antigen, CD4 antigen, etc.

SI-6. Analysis of reserch topics in mRNA vaccine patents
From the distribution of patent research topics, the global mRNA vaccine field focuses on coronavirus vaccine research, tumor vaccine research, nucleic acid vaccine research, and other aspects (Figure S7).In the case of viral vaccines (red dots), key concepts include severe acute respiratory syndrome coronavirus 2, middle east respiratory syndrome related coronavirus), influenza vaccines, and others.Key concepts for cancer vaccines include lung neoplasm, mammary gland neoplasm, prostate gland neoplasm, indicating these diseases may be the focus of mRNA-based cancer vaccine development (green dots).From the distribution of patent research topics, the global field of mRNA modification focuses on drug delivery types, carrier materials, nucleic acid modification, mechanism research, and other aspects (Supplemental Figure S8).Among them, in terms of the type of administration, key concepts include intraperitoneal injections, pharmaceutical intravenous injections, subcutaneous injections, etc.With regards to carrier materials, nanoparticles are infused with cationic lipids, pharmaceutical nanoparticles, pharmaceutical liposomes, etc. Nucleic acid modifications include oligonucleotide analogs, nucleotide analogs, peptide nucleic acids, etc.In terms of mechanism research, key concepts include transcription, growth factors, and membrane proteins, etc.  S1 show the countries and the organizations, respectively, with the most patents related to mRNA modifications.

Figure S2 .
Figure S2.Global annual publications of patents related to mRNA vaccines

Figure S3 .
Figure S3.Global annual publications of patents related to mRNA delivery systems.Note: An estimated value (empty part) was provided for October through December of 2022 based the data collected up to the end of September (solid part).

Figure S4 .
Figure S4.Global annual publication of patents related to mRNA modifications

Figure S5 .
Figure S5.Distribution of topics in patents related to mRNA therapeutics

Figure S6 .
Figure S6.Distribution of topics in patents related to mRNA delivery systems

Figure S7 .
Figure S7.Distribution of topics in patents related to mRNA vaccines

Figure S8 .
Figure S8.Distribution of topics in patents related to mRNA modification

Figure S9 .
Figure S9.Top five countries with patents related to mRNA modifications

Table S1 .
Organizations with most patents related to mRNA modifications