mRNA technology promises to revolutionize future vaccines

More than 80 million Americans have been vaccinated against SARS-CoV-2 — the virus that causes COVID-19 — using the game-changing possibilities of mRNA technology. And while some people worry that the technology has been “rushed,” for more than 25 years university labs have been exploring the use of RNA, rather than viruses, to build the body’s immunity against diseases…

Messenger RNA (mRNA) — the basis of the first two vaccines cleared for public use by the Food and Drug Administration — induces cells to set off an immune response against the coronavirus that causes COVID-19. Vaccine researchers believe the success of these inoculations will usher in the most radical change to vaccine development since Jenner tapped a cow virus two centuries ago.

mRNA emerged as an alternative to traditional vaccine development in the early 1990s, building on research involving RNA injections into mice at the Waisman Center at the University of Wisconsin-Madison. mRNA is a molecule that essentially delivers instructions to cells to build specific proteins. Proteins are key to the success of a viral infection, because they enable a virus to replicate after it attaches to a cell. The coronavirus, for example, attaches to a cell with a so-called “spike” protein, which triggers the viral replication that turns the infection into COVID-19.

The theory behind the vaccines is that mRNA will tell a cell to make a protein that’s used by a certain virus, which would set off an immune response that builds the body’s ability to fend off the actual virus.

“It’s essentially biological software,”…says John Cooke, MD, PhD, medical director of the RNA Therapeutics Program at the Houston Methodist Research Institute.

Yes, it really is that simple to explain. That simplicity is part and parcel of time saved, costs lowered, for the design of production-ready vaccines.

A man was reinfected with coronavirus after recovering…!

May James/AFP/Getty

A 33-year old man was found to have a second SARS-CoV-2 infection some four-and-a-half months after he was diagnosed with his first, from which he recovered. The man, who showed no symptoms, was diagnosed when he returned to Hong Kong after a trip to Spain.

There is no published peer-review report on this man – only a press release from the University of Hong Kong – although reports say the work will be published in the journal Clinical Infectious Diseases.

The author, Megan Culler Freeman, asks and answers questions raised by the news reports.

Some plants talk to each other on the genetic level

“So, how do you feel about tendril sex?”

Whether or not plants hear and talk to us, they sure talk among themselves – some of them, at least. This has been established by scientific research in the past: plants communicate to each other via signals in the form of chemicals. Some species of plants, in fact, have sophisticated means of interacting with others of their kinds: while some can share genetic information, others send warning messages of possible insect attacks. The former form of communication entails parasitic plants attaching onto their hosts.

Dodder, which is a parasite, attaches onto the other plant known as Arabidopsis, stealing some of its nutrients in the process via an appendage. However, to have their meal of nutrients, Dodder has to first identify its host. It was previously thought that it uses chemicals to do so. Now, a new study has demonstrated that dodder uses a genetic method: it exchanges RNA with the plant. These two plants thereby ‘talk’ to each other as they exchange pieces of mRNA.

What do they say to each other then? Mystery, mystery. Perhaps, Dodder signals its host to ‘allow’ it to drain its nutrients by tricking it to lower its defenses?

The picture says it all.

Thanks, Mike

You say tomato – I say comparative transcriptomics

Brad Townsley/UC Davis

You say tomato, I say comparative transcriptomics. Researchers in the U.S., Europe and Japan have produced the first comparison of both the DNA sequences and which genes are active, or being transcribed, between the domestic tomato and its wild cousins.

The results give insight into the genetic changes involved in domestication and may help with future efforts to breed new traits into tomato or other crops, said Julin Maloof…senior author on the study.

For example, breeding new traits into tomatoes often involves crossing them with wild relatives. The new study shows that a large block of genes from one species of wild tomato is present in domestic tomato, and has widespread, unexpected effects across the whole genome…

Among other findings, genes associated with fruit color showed rapid evolution among domesticated, red-fruited tomatoes and green-fruited wild relatives. And S. pennellii, which lives in desert habitats, had accelerated evolution in genes related to drought tolerance, heat and salinity…

New technology is giving biologists the unprecedented ability to look at all the genes in an organism, not just a select handful. The researchers studied not just the plants’ DNA but also the messenger RNA being transcribed from different genes. RNA transcription is the process that transforms information in genes into action. If the DNA sequence is the list of parts for making a tomato plant, the messenger RNA transcripts are the step-by-step instructions…

“We could not have done a study like this ten years ago — certainly not on any kind of reasonable budget,” Maloof said. “It opens up a lot of new things we can do as plant scientists.”

Bravo! Like anyone who has Mediterranean genes – and cooking – in their life, I have an inordinate interest in tomatoes.

I grew up in a New England factory town with tomatoes in the backyard garden. I live in the high desert country of New Mexico with tomatoes in our courtyard garden. I cook with fresh, dried, canned and whatever kind of tomatoes I can get hold of any time of the year.

They’re all delicious and all good for me – as far as I’m concerned.

Leicester scientists print out the human genome in 130 volumes

An exhibition on genomics – the study of genetic material which is driving major medical research innovations – has opened at Leicester’s New Walk Museum.

Inside DNA: A Genomic Revolution offers people the chance to learn more about genome research and have a say in the future policy of the science…

The University of Leicester’s Department of Genetics has printed out an entire human genome – amounting to 130 volumes of some 300 pages – which is going on display at the museum.

The work has been done by the Genetics Education Networking for Innovation and Excellence (Genie), based at the university.

Genie spokesman Dr Cas Kramer said: “Genie’s outreach programme has enabled us to develop workshops to further enhance the Inside DNA exhibit and we are very much looking forward to working with the museum over the next six months.”

Clare Matterson, from the Wellcome Trust, which funds the exhibition, said: “Over a decade since the first human genome was published, scientists are starting to get to grips with what the information in our DNA means for health and disease.

“Inside DNA is more relevant than ever, giving people a chance to explore issues raised by this research.”


Computer assisted design, CAD for RNA, synthetic biology

The computer assisted design (CAD) tools that made it possible to fabricate integrated circuits with millions of transistors may soon be coming to the biological sciences. Researchers at the U.S. Department of Energy (DOE)’s Joint BioEnergy Institute (JBEI) have developed CAD-type models and simulations for RNA molecules that make it possible to engineer biological components or “RNA devices” for controlling genetic expression in microbes. This holds enormous potential for microbial-based sustainable production of advanced biofuels, biodegradable plastics, therapeutic drugs and a host of other goods now derived from petrochemicals.

“Because biological systems exhibit functional complexity at multiple scales, a big question has been whether effective design tools can be created to increase the sizes and complexities of the microbial systems we engineer to meet specific needs,” says Jay Keasling, director of JBEI…“Our work establishes a foundation for developing CAD platforms to engineer complex RNA-based control systems that can process cellular information and program the expression of very large numbers of genes. Perhaps even more importantly, we have provided a framework for studying RNA functions and demonstrated the potential of using biochemical and biophysical modeling to develop rigorous design-driven engineering strategies for biology…”

Synthetic biology is an emerging scientific field in which novel biological devices, such as molecules, genetic circuits or cells, are designed and constructed, or existing biological systems, such as microbes, are re-designed and engineered. A major goal is to produce valuable chemical products from simple, inexpensive and renewable starting materials in a sustainable manner. As with other engineering disciplines, CAD tools for simulating and designing global functions based upon local component behaviors are essential for constructing complex biological devices and systems. However, until this work, CAD-type models and simulation tools for biology have been very limited…

JBEI researchers are now using their RNA CAD-type models and simulations as well as the ribozyme and aptazyme devices they constructed to help them engineer metabolic pathways that will increase microbial fuel production. JBEI is one of three DOE Bioenergy Research Centers established by DOE’s Office of Science to advance the technology for the commercial production of clean, green and renewable biofuels. A key to JBEI’s success will be the engineering of microbes that can digest lignocellulosic biomass and synthesize from the sugars transportation fuels that can replace gasoline, diesel and jet fuels in today’s engines…

While the RNA models and simulations developed at JBEI to date fall short of being a full-fledged RNA CAD platform, Keasling, Carothers and their coauthors are moving towards that goal.

Cripes. Twenty-eight years ago I thought it was a big deal when I was instructing users on AutoCAD. Adding new modules to layout the drainage of subdivisions and recycle rainwater was finally possible with the horsepower we finally had in AT-level desktop computers. Woo-hoo! 🙂

Folks getting into the next generations of computational analysis are going to think they’re in a new dimension.

Dangerous bacterium hosts intermediary genetic remnant

Nope. No angels on pinheads.

Within a dangerous stomach bacterium, Yale University researchers have discovered an ancient but functioning genetic remnant from a time before DNA existed.

To the surprise of researchers, this RNA complex seems to play a critical role in the ability of the organism to infect human cells, a job carried out almost exclusively by proteins produced from DNA’s instruction manual.

“What these cells are doing is using ancient RNA technology to control modern gene expression,” said Ron Breaker…investigator for the Howard Hughes Medical Institute and senior author of the study.

In old textbooks, RNA was viewed simply as the chemical intermediary between DNA’s instruction manual and the creation of proteins. However, Breaker’s lab has identified the existence and function of riboswitches, or RNA structures that have the ability to detect molecules and control gene expression – an ability once believed to be possessed solely by proteins. Breaker and many other scientists now believe the first forms of life depended upon such RNA machines, which would have had to find ways to interact and carry out many of the functions proteins do today.

The new paper describes the complex interactions of two small RNA molecules and two larger RNA molecules that together influence the function of a self-splicing ribozyme, a structure many biologists had believed had no role other than to reproduce itself. The new study, however, suggests that in the pathogenic stomach bacterium Clostridium difficile, this RNA structure acts as a sort of sensor to help regulate the expression of genes, probably to help the bacterium manipulate human cells.

“They were though to be molecular parasites, but it is clear they are being harnessed by cells to do some good for the organism,” Breaker said.

This is the sort of RNA structure that would have been needed for life existing before the evolution of double-stranded DNA, with its instruction book for proteins that carry out almost all of life’s functions today.

Interesting research – of the chicken or egg variety.

Sooner or later, the research will appear on a free site for us ordinary mortals to wander through.

Origin of Life: RNA molecules forming in warm water

A key question in the origin of biological molecules like RNA and DNA is how they first came together billions of years ago from simple precursors. Now, in a study appearing in this week’s JBC, researchers in Italy have reconstructed one of the earliest evolutionary steps yet: generating long chains of RNA from individual subunits using nothing but warm water.

Many researchers believe that RNA was one of the first biological molecules present, before DNA and proteins; however, there has been little success in recreating the formation on RNA from simple “prebiotic” molecules that likely were present on primordial earth billions of years ago.

Now, Ernesto Di Mauro and colleagues found that ancient molecules called cyclic nucleotides can merge together in water and form polymers over 100 nucleotides long in water ranging from 40-90 °C –similar to water temperatures on ancient Earth…

This finding is exciting as cyclic nucleotides themselves can be easily formed from simple chemicals like formamide, thus making them plausible prebiotic compounds present during primordial times. Thus, this study may be revealing how the first bits of genetic information were created.

Surprising a few generations of True Believers, as well, who presumed scientists would find nano-angels pushing these bits of molecules together to form RNA chains.