I’ve given DNA a lot of love over the years -- DNA as a storage medium, as a computing platform, as the basis for robots, as the tool for synthetic biology/biohacking, even used for the DNA-of-Things (DoT). DNA is the basis for all life as we know it, in every category of life we’ve found anywhere on earth. That we are now using it to achieve technological goals seems like one of humankind’s greatest accomplishments.
But where’s the love for RNA, DNA’s putative ancestor and still-partner? A few recent developments in RNA caught my eye that I wanted to give their due.
As you may remember from high school biology, RNA has
a crucial role in how DNA transmits genetic information. As one source explains
it: “DNA holds information,
but it generally does not actively apply that information. DNA does not make things.”
Instead, it transcribes the information onto RNA, which then actually
makes things happen.
Just last week
researchers from Northwestern University were
able to show RNA switching genes off and on, using a simulation model they “affectionately”
call R2D2 (short for “reconstructing
RNA dynamics from data”). The
researchers believe the “strand displacement” mechanism is what switches genes “on”
or “off.”
Professor Julius B. Lucks, who co-led the research, believes:
“Many diseases are likely caused
by something going awry at the RNA level.
The more we know about this, the better we can design RNA targeting
drugs and RNA therapeutics.” For
example, genes could be “engineered to turn “on” in the presence of an
environmental contaminant.”
Amazing stuff. But that’s not all.
Researchers at the University of Tokyo have created an RNA
molecule that can not just replicate but evolve. There has long been a hypothesis, called “RNA
World,” which speculates that RNA is the basis for the origin of life, with
DNA coming along at some later point (DNA is believed not to be stable enough to
survive, much less evolve, in the primordial environment). The research makes that hypothesis even more
plausible.
The results were somewhat surprising, even to the
researchers. “Honestly, we initially
doubted that such diverse RNAs could evolve and coexist,” said Ryo Mizuuchi,
corresponding author of the study.
We will probably never know how life on earth actually emerged, but the researchers claim:
Our results demonstrate an evolutionary transition scenario of molecular replicators from a single common ancestor to a multi-membered network…Thus, our simple experimental setup offers a unique approach to deeply look into evolutionary phenomena.
OK, that’s two long-time mysteries answered, or at
least addressed, by RNA. Here’s an even
more fun one: RNA computers.
There has been discussion of DNA computers for many years. However, as NIST (National Institute of Standards and Technology) says:
Tiny biological computers made of DNA could revolutionize the way we diagnose and treat a slew of diseases, once the technology is fully fleshed out. However, a major stumbling block for these DNA-based devices, which can operate in both cells and liquid solutions, has been how short-lived they are. Just one use and the computers are spent.
Instead, in a new paper, NIST researchers used RNA to build computers. Or, more precisely:
Here, we develop scalable cotranscriptionally encoded RNA strand displacement (ctRSD) circuits that are rationally programmed via base pairing interactions. ctRSD circuits address the limitations of DNA-based strand displacement circuits by isothermally producing circuit components via transcription.
Samuel Schaffter, the lead author and a NIST postdoc
researcher, explained
how DNA and RNA computing differs from typical computing: “The difference is,
instead of coding with ones and zeroes, you write strings of A, T, C and G,
which are the four chemical bases that make up DNA.” The authors tested whether the RNA-based circuits
could perform logical operations (I won’t even attempt to describe exactly how
they did this).
Dr. Schaffter said:
“For me, these needed to work in a test tube as predictively as DNA computing.
The nice thing with DNA circuits is most of the time, you can just write out a
sequence on a piece of paper, and it'll work the way you want. The key thing
here is that we did find the RNA circuits were very predictable and
programmable, much more so than I thought they would be, actually.”Credit: Shaffter and Strychalski
The authors are quite excited about future
applications. E.g., “We envision ctRSD
circuits enabling many new applications in nucleic acid computing and synthetic
biology. For example, the inclusion of ribonucleases in ctRSD circuits would
allow continuous circuit turnover. Circuits could then respond multiple times
to changing input signals, overcoming a current challenge in DNA computing.”
As for the next step, Dr. Schaffter sees:
“We’re interested in putting these in bacteria next. We want to know: Can we
package circuit designs into genetic material using our strategy? Can we get
the same sort of performance and behavior when the circuits are inside cells? We
have the potential to.”
I can’t wait for Raspberry
Pi to come out with their RNA-based computer. You watch.
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All this sounds very esoteric and perhaps not applicable to the immediate woes of our healthcare system, but I’m thinking about the rest of the 21st century and beyond. As I’ve said before, the 20th century may have been the age of computers, but the 21st century is going to be the age of biology.
If we believe that the 20th
century ushered in “modern medicine,” with more rigorously trained
professionals using more scientific tools (think antibiotics, imaging, laparoscopic
surgeries, A.I., etc.), then 21st century healthcare is going to be
about synthetic
biology. Thinking about DNA and RNA
isn’t going to just be something healthcare professionals do to satisfy their
undergraduate requirements; it’s going to be integral to their toolset.
What’s going to be very
interesting – and highly disruptive -- is not just how this change will impact
our health and our healthcare, but also what happens to physicians, nurses,
pharmacies in a world where biologists/biochemists/geneticists may play the
more important role.