Talk:Timeline of mRNA research

Review by Vipul on 2024-10-05

Standalone evaluation

Line-by-line comments

• You have what seem to be duplicate rows for the Pfizer vaccine approval.✔
• The significance of the rows on the other types of RNA, specifically transfer RNA (tRNA) and ribosomal RNA (rRNA) for a timeline of mRNA research are not clear. It may be worth either elucidating how they are related, either within the timeline rows or via an explainer on top.✔(Sebastian: I removed the rows from the timeline)
• Can you double-check if the two rows on Nirenberg and Matthaei (one for a publication, and one for a discovery) are talking about the same thing or overlapping things?✔

Overall comments

• A bit more scientific background and explainer might help (this overlaps with my line-by-line comment about the other types of RNA). Are we talking about the mRNA of humans (the hosts whom we are trying to keep healthy) or the bacteria or viruses that are attacking the host? What are the other alternative approaches that mRNA may be displacing?✔ (Sebastian: clarified at the introduction and inclusion criteria sections)
• I'd like to see more coverage of the angles of criticism and skepticism of mRNA research, particularly the mRNA vaccine strategy, both in popular discourse and the scientific community. What has created the perception that mRNA vaccines may be risky? Is it just that they're new, or are there specific things in their mechanism? Conversely, what makes many people take the view that mRNA vaccines (/ other therapies) are inherently less risky?✔ (Sebastian: according to what I've read, it's mostly the early approval of mRNA vaccines the main issue. Also cardiovascular complications found)
• Sebastian: I made a number of additional improvements, including updates on the numerical and visual data section.

External evaluation

I asked ChatGPT for a timeline of mRNA research and it produced something that roughly matched a subset of this timeline.

Extended timeline

Year	Condition (when applicable)	Event type	Details	Location
1958		Nomenclature	RNA-rich microsomal particles are baptised "ribosomes", during informal discussions at a conference. This term is coined to describe these cellular structures, which play a crucial role in protein synthesis. Ribosomes are composed of ribosomal RNA (rRNA) and proteins, and they function as the sites where mRNA is translated into proteins. The naming and subsequent research into ribosomes significantly advances our understanding of cellular processes and the molecular machinery involved in translating genetic information into functional proteins. This breakthrough lays the foundation for further studies in molecular biology and genetics.
1961		Discovery	In what would be known as the Nirenberg and Matthaei experiment, Marshall Warren Nirenberg and J. Heinrich Matthaei decipher the first codon, UUU, as coding for the amino acid phenylalanine. This pivotal discovery marks a significant milestone in molecular biology, providing the first insights into the genetic code that translates the information encoded in mRNA into proteins. By using a synthetic RNA composed of uracil nucleotides, they demonstrate how specific sequences of nucleotides correspond to particular amino acids, ultimately leading to the synthesis of proteins. This work lays the foundation for understanding the genetic code and the process of translation, profoundly impacting genetics and biochemistry.	United States (National Institutes of Health)
1970		Discovery	Significant advancements are made in understanding the role of transfer RNA (tRNA) in protein synthesis. Researchers elucidate how tRNA facilitates translation, a key step in the process of converting genetic information from messenger RNA (mRNA) into proteins. tRNA molecules act as adaptors, bringing specific amino acids to the ribosome, the cellular machinery responsible for protein assembly. This discovery clarifies how genetic instructions are translated into functional proteins and contributes to the broader understanding of molecular biology. The insights gained from studying tRNA would have profound implications for genetics, biochemistry, and medicine.
1983	Gene expression	Discovery	Researchers make a significant discovery by identifying two key features of mRNA: the 5' cap and the 3' polyadenylation. The 5' cap, a modified guanine nucleotide added to the beginning of the mRNA molecule, and the 3' polyadenylation, a tail of adenine nucleotides added to the end, are found to be essential for mRNA stability and the initiation of translation. These modifications protect mRNA from degradation, assist in the export of mRNA from the nucleus, and are crucial for the efficient initiation of protein synthesis. This discovery is pivotal in understanding the regulation of gene expression at the mRNA level.
1991	Cancer therapy	Therapeutic development	mRNA is proposed as a potential active pharmaceutical ingredient for the treatment of cancer. This idea emerges from the growing understanding of mRNA's role in protein synthesis and its potential to be harnessed for therapeutic purposes. The concept involves using mRNA to instruct cells to produce proteins that can stimulate an immune response against cancer cells or directly target and attack tumor cells. This proposal marks an early recognition of mRNA's potential in cancer therapy, paving the way for subsequent developments in the use of mRNA for targeted treatments and immunotherapies in oncology. This experiment demonstrates the ability of mRNA to produce proteins in vivo, establishing its potential as a therapeutic tool for replacing defective or missing proteins in genetic disorders.
1996	Gene regulation and therapeutics	Discovery	RNA interference (RNAi) is discovered, revealing a mechanism in which small RNA molecules regulate gene expression. This groundbreaking discovery would revolutionize molecular biology and earn the Nobel Prize in Physiology or Medicine in 2006 for its discoverers Andrew Fire and Craig Mello. RNAi would since become a crucial tool in scientific research, enabling precise control over gene expression and offering promising applications in therapeutics, agriculture, and biotechnology.
1998		Discovery	A small interfering RNA (siRNA) or micro RNA (miRNA), is discovered as a class of naturally occurring RNA. This discovery, made by MK and Kostas, reveals that siRNA and miRNA play a crucial role in the post-transcriptional machinery of cells. By targeting specific mRNAs, siRNA and miRNA can form double-stranded RNA molecules that prompt rapid degradation (known as gene silencing). Consequently, this mechanism offers the potential to regulate gene expression at a post-transcriptional level. The utilization of siRNA and miRNA holds promise in the development of treatments for HIV, cancer, and melanoma.
2005		Vaccine development	The U.S. Food and Drug Administration (FDA) grants approval for the first mRNA-based vaccine, specifically for rabies in animals. This milestone demonstrates the potential of mRNA technology in vaccine development. The approval marks a significant advancement, showcasing mRNA's ability to generate an immune response by instructing cells to produce proteins that are essential for fighting the virus. This early success paves the way for subsequent development of mRNA vaccines for humans, including those for COVID-19, and highlights the versatility and promise of mRNA technology in combating infectious diseases.	United States
2006 (March 26)	Gene therapy	Experiment	A significant breakthrough is achieved in the field of gene therapy through monkey studies. Researchers conduct experiments using a lipid nanoparticle system to successfully deliver RNA and silence disease-causing genes. This achievement demonstrates the potential of this novel approach for gene therapy. The successful delivery of RNA using the lipid nanoparticle system in monkey studies would pave the way for future advancements in the field of RNA-based therapeutics. The research is conducted under the auspices of Protiva Biotherapeutics, a company at the forefront of developing innovative solutions in the field of gene therapy.
2017–2019	Infectious disease treatments	Scientific advancement	Significant advancements are achieved in the effectiveness of mRNA encoding antibodies against HIV and rabies, as evidenced by studies conducted by Pardi et al., Thran et al., and Schlake et al. in 2019. These studies contribute to the growing understanding of the potential of mRNA-based approaches in combating these infectious diseases.
2018	Amyloidosis	FDA approval	U.S. FDA approves mRNA-based therapeutics against hereditary ATTR amyloidosis. This condition involves the accumulation of abnormal amyloid proteins in tissues and organs, leading to severe and potentially life-threatening complications. The approval of these mRNA therapeutics represents a significant breakthrough, utilizing mRNA technology to address the genetic root of the disease. By instructing cells to produce proteins that counteract the effects of the amyloid deposits, these treatments aim to slow or halt the progression of the disease, offering new hope for patients affected by this rare and challenging condition.	United States