DNA molecules are highly programmable.
By folding DNA into a virus-like structure, MIT researchers have designed HIV-like particles that provoke a strong immune response from human immune cells grown in a lab dish. Such particles might eventually be used as an HIV vaccine.
Exploring how a small change in your DNA sequence can make you a natural blonde.
A few weeks after preparing them, Dr Catherine Guenther checked her mouse embryos and knew that she had identified the source of a blond-haired mutation in human DNA.
The National Institutes of Health hopes synthetic biology can engineer vaccines that outperform nature.
- The first coronavirus vaccines will enter Phase 2 testing soon but won't be ready for another 18 months.
- Synthetic biology may offer a "universal coronavirus vaccine" that can be quickly modified to combat future mutated forms.
- Despite promising lab tests, synthetic vaccines remain speculative; we'll need to live with COVID-19 during the interim.
Engineering a solution<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjg3MTkwOC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1MDM4Mzc2OX0.4ajk0E5MhiYOCCFS4EJ30lPxDjbv5DQ-Z8mokpW05F8/img.jpg?width=1245&coordinates=0%2C413%2C0%2C414&height=700" id="0d1b5" class="rm-shortcode" data-rm-shortcode-id="9119460af46af239b5f3084e50fa2b62" data-rm-shortcode-name="rebelmouse-image" />
A synthetic biology research laboratory at NASA Ames.
A recent computer analysis found that millions of possible chemical compounds could be used to store genetic information. This begs the question — why DNA?
- The central dogma of biology states that genetic information flows from DNA to RNA to proteins, but new research suggests that this may not be the only way for life to work.
- A sophisticated computer analysis revealed that millions of other molecules could be used to function in place of the two nucleic acids, DNA and RNA.
- The results have important implications for developing new drugs, the origins of life on Earth, and its possible presence in the rest of the universe.
Millions of useful targets<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjA5NjIyNi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1ODg0NDk0Mn0.rpHB0peVqFgd81OKVLnwACp7dWaL0WaOZ1ZKHyxt_kA/img.jpg?width=980" id="99405" class="rm-shortcode" data-rm-shortcode-id="cc8bc3f6d09d7a99bba5a83604b20140" data-rm-shortcode-name="rebelmouse-image" alt="Central dogma of biology" />
The central dogma of biology asserts that the genetic information is transcribed from DNA to RNA, which then translates that information into useful products like proteins. This new research, however, suggests that DNA and RNA are just two options out of millions of others.
Shutterstock<p>Analogues to nucleic acids exist, many of which serve as the foundation for important drugs for treating viruses like HIV and hepatitis as well as for treating cancers, but until recently, no one was sure of how many unknown nucleic acid analogues could be out there.</p><p>"There are two kinds of nucleic acids in biology," said <a href="https://phys.org/news/2019-11-dna-millions-genetic-molecules.html" target="_blank">co-author Jim Cleaves</a>, "and maybe 20 or 30 effective nucleic acid-binding nucleic acid analogues. We wanted to know if there is one more to be found or even a million more. The answer is, there seem to be many more than was expected."</p><p>Cleaves and colleagues decided to conduct a chemical space analysis — in essence, a sophisticated computer technique that generates all possible molecules that adhere to a set of defined criteria. In this case, the criteria were to find compounds that could serve as nucleic acid analogues and as a means of storing genetic information.</p><p>"We were surprised by the outcome of this computation," said co-author Markus Meringer. "It would be very difficult to estimate a priori that there are more than a million nucleic acid–like scaffolds. Now we know, and we can start looking into testing some of these in the lab."</p><p>Though no specific analogues were targeted in this paper, it does present a long list of candidates to be explored for use as drugs for serious diseases like HIV or cancer. A more intriguing possibility suggested by the research is that life itself may have taken its very first steps using one of these alternative compounds.</p><p>Many scientists believe that before DNA became the dominant means of storing genetic information, life used RNA to code genetic data and pass it down to offspring. In part, this is because RNA can <a href="https://www.news-medical.net/life-sciences/What-is-the-RNA-World-Hypothesis.aspx" target="_blank">directly produce</a> proteins, which DNA can't do on its own, and because it's a simpler structure than DNA. Over time, life likely started to opt for using DNA for storage due to its greater stability and to rely on RNA as a kind of middleman for producing proteins. But RNA on its own is still a <a href="https://phys.org/news/2013-12-scientists-closer-rna.html" target="_blank">very complicated</a> compound and is fairly unstable; in all likelihood, something simpler came before RNA, possibly using some of the nucleic acid analogues identified in this study.</p>
A galaxy of nucleic acid analogues<p>Not only does this shed light on how life may have started on Earth, but it also has implications for alien life as well. Co-author Jay Goodwin said, "It is truly exciting to consider the potential for alternate genetic systems based on these analogous nucleosides — that these might possibly have emerged and evolved in different environments, perhaps even on other planets or moons within our solar system. These alternate genetic systems might expand our conception of biology's 'central dogma' into new evolutionary directions, in response and robust to increasingly challenging environments here on Earth."</p><p>When we search for extraterrestrial life, often we're looking for signs of RNA and DNA, but this may be an excessively narrow scope. After all, if millions of alternatives exist, there would need to be something very special indeed for life to universally favor using just DNA and RNA.</p>
The FDA calls out creators of genetically tweaked hornless bulls.
- Hornless bull clones turn out to have questionable genomes.
- Scientists were so confident they didn't even look for transgenic DNA.
- No one's sure what to do with the offspring.
The arrival of Spotigen and Buri<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE1Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwMzUzNDgxOX0.FncQraghoKRg6Kz4tj6XS2osmzY_GroWyWTpz4jHYds/img.jpg?width=980" id="e8da5" class="rm-shortcode" data-rm-shortcode-id="b19d6c0ae8f91f802036bfab1c873ac9" data-rm-shortcode-name="rebelmouse-image" />
Image source: ANGHI/Shutterstock/Big Think<p>Recombinetics' bulls were heralded examples of gene modification's potential. Farmers regularly "poll" cows — that is, remove their horns— in a painful, difficult process aimed at preventing accidental injuries in herds and the humans that tend them.</p><p>The company used TALENs gene editing ("Transcription Activator-Like Effector Nucleases) to swap out a section of about 200 genes from a Holstein dairy bull for genes from a hornless one.</p><p>DNA editing involves cutting DNA with enzymes called nucleases targeted at the desired location in a cell's genome. Nucleases are proteins, which are hard to work with, so many researchers — including Recombinetics' — instead introduce plasmids, circular mini-chromosomes that code for the required "scissor." This causes the target cell to produce the nucleases itself, sparing the scientists the complexities of dealing with unstable protein.</p><p>In the case of Recombinetics' bulls, the plasmids also contained the replacement hornless DNA for insertion at the cut. Coming along for the ride — unknown to Recombinetics — was transgenic DNA, including the antibiotic-resistant genes and a handful of other things from a range of diverse microbes. This wouldn't necessarily have been a problem if the plasmids hadn't unexpectedly inserted themselves into the target cell's genome instead of simply delivering their payload and being done, as planned. Thus, adjacent to its edit site were <a href="https://www.independentsciencenews.org/health/gene-editing-unintentionally-adds-bovine-dna-goat-dna-and-bacterial-dna-mouse-researchers-find/" target="_blank">4,000 base pairs</a> of DNA that from the plasmid.</p>
Over-confident<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNDM1MTE4MX0.dfyGyeHtjCpNogRkwv3-UZHBAQ3dpFnOKtXRd-STK50/img.jpg?width=980" id="0a22f" class="rm-shortcode" data-rm-shortcode-id="4af032e6384db1af6345d8d74d1b3331" data-rm-shortcode-name="rebelmouse-image" />
Image source: wikimedia/U.S. Food and Drug Administration<p>At the time the editing was first announced, Recombinetics was very confident that what they'd produced was "100% bovine." "We know exactly where the gene should go, and we put it in its exact location," claimed Recombinetics to <a href="https://www.bloomberg.com/news/articles/2017-10-12/this-genetics-company-is-editing-horns-off-milk-cows" target="_blank">Bloomberg</a> in 2017. "We have all the scientific data that proves that there are no off-target effects." In response to the latest findings, however, Tad Sontesgard of the Recombinetics subsidiary that owns the animals, admitted, "It was not something expected, and we didn't look for it." He acknowledges a more thorough examination of their work "should have been done."</p><p>Since genetically edited animals may be consumed, the FDA's position is that they likely require thorough testing and approvals. Recombinetics has publicly complained about such hurdles standing in the way of making animal genetic editing a routine occurrence. (They've also developed piglets that never hit puberty.) The company attempted to <a href="https://www.technologyreview.com/s/610027/farmland-gene-editors-want-cows-without-horns-pigs-without-tails-and-business-without/" target="_blank">convince the Trump Administration</a> to take genetically altered animals away from under the FDA.</p>
How the problem was found<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE2NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyMDA3NzAyMX0.SBCvmAAsWaDYU7dkPQ7CgcrtQovHK-MWvOizZUCZqQg/img.jpg?width=980" id="43f50" class="rm-shortcode" data-rm-shortcode-id="6f28fb809a618ce4383b7cb4942805fb" data-rm-shortcode-name="rebelmouse-image" />
Image source: Moving Moment/Shutterstock<p>Not surprisingly, Recombinetics never applied for approval with the FDA, but Alison Van Eenennaam, their collaborator from University of California, Davis, did inform the FDA of their existence to facilitate exchanges of research insights and data.</p><p>Since the surviving edited cattle were being put up at Davis, Eenennaam started thinking about what to do with them. Incinerating experimental animals — and each of these weighs about a ton — costs 60 cents per pound. On the other hand, turning them into hamburger and steaks could reverse that cash flow. Her attempt to win the cows a food exemption from the FDA led to the discovery of the plasmids, though Sontesgard <a href="https://www.technologyreview.com/s/614235/recombinetics-gene-edited-hornless-cattle-major-dna-screwup" target="_blank">asserts</a> they'd be safe to eat in either case.</p><p>And then there's milk. Brazil agreed to raise the first herd of genetically modified hornless dairy cows. Regulators there had even determined no exceptional oversight was going to be required.</p><p>Soon a bioinformatician from the FDA stumbled across the plasmid in a bull's genome. It's estimated that about half of Buri's 17 offspring also have it in theirs. The cows are now absolutely classified as genetically modified organisms, GMOs, not pure cow. Brazil has backed out.</p>
Slowing their roll<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMTE2MTE2OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNzcxMDgxMn0.VmwCM6ss3JJ0-imNVggLLjNviBpY5KhHIuz7CtxvaMs/img.jpg?width=980" id="22429" class="rm-shortcode" data-rm-shortcode-id="0ad6c70f0e27fe6d94516a01cb5fb35f" data-rm-shortcode-name="rebelmouse-image" />
Image source: Sergey Nivens/Shutterstock<p> As science moves forward a few steps, it often has to back up a step or two. Glimpsing a solution, especially to such a complex problem as genome editing, isn't the same as having one fully in hand, no matter how attractive the reward of getting there first may be, or how much money is to be made. We're on the edge of a new frontier here, and there are a growing number of similar tales. Scientists do need courage to stretch the boundaries of the known, yes, but humility is also a good idea.</p>