Another method is called RNAi. Instructions for your cell development are transcripted from your genome into molecules called RNA, which are then translated into proteins. But RNAi does more than just act as a messenger betwen the DNA and the proteins. Itb can move in reverse and create DNA, like the virus enzyme RNA reverse Transcriptase. It can direct amino acids to their targest, like TtRNA. Or iot can take part in RNA interference or RNAi. But why would RNA want to interfere with itself? Well, sometimes a cell doesn’t want to turn all of the messenger RNA it creates into protein. Or it may need to destroy RNA inhjected into the cell by an attacking virus. When the cell find s or produces long or double stranded RNA molecules, it chops the molecules up with a protein named DICER. These short snuippets of RNA are floating around in the cell and are picked up by something called RISK, the RNA silencing complex. It is picked up by a protein named Slicer. RISK stripps small chunks of dsRNA in half, using a single strand to target matching mRNA, looking for pieces that fit together like two halves of a sandwich, when it finds the matching piece of mRNA, RISK’s slicer protein slieces it up[, the cell then realizes there are odd strangely sized pieces of RNA flying around, preventing the mRNA from being turned into protein. So you have dsRNA, you dice it up, it targets mjRNA, and that gets sliced up too. Voila, you’ve prevented expression and saved some energy. The process was first discovered in petunias, where scientists trying to create deep purple blooms, introduced a pigment producing gene into the flowers. But instead of darker flowers, they found flowers with white patches and no pigment at all. Instead of using the RNA produced by the new gene to create new pigment, the theThe flowers were actually using it to knock down the pigment producing patheway, destroying RNA from the plant’s original genes with RNAi, and leaving them with pigment free white flowers. Scientists saw a similar phenomena in tiny worms called C Elegans. Once they figured out what was happening, they realized they could use RNAi to their advantage. They can see what happens when a certain gene is knocked out in a worm or a fly.=? Introduce an RNAi construct for that gene and BAM, no more protein expression. You can even get creative and target that effect to certain systems, knocking down genes in just the brain or just the liver or just the heart. Fiuguing out what happens when you knock out a gene in a certain system is an iomportant system in figuring out what a gene does, it can also be a powerful therapeutic tool. It could be a way for us to manipulate what is happneing within our own cells. Researchers have targeted RNA in tumor cells in the hopes of turning off cancer causing genes.
A CRISPR SYSTEM FOR RNA
The future of genetic modification lies in CRISPR. This gene-editing technique, remarkable as much for its simplicity as for its effectiveness, “snips” sections of genetic sequences apart in order to insert newer strands of genetic code. Apart from hypothetically being able to enhance the human genome by adding in customized genetic code, several studies have shown that it can even remove the HIV genome from infected cells – albeit with mixed results.
Now, a new study published in the journal Science has revealed that it’s not just DNA that CRISPR can manipulate and edit; RNA, which some see as the primitive “precursor” molecule to DNA, and the genetic code of many types of viruses, is now also a legitimate target for the CRISPR technique.
Introducing C2c2. Broad Institute via YouTube
Although researchers have long been able to “interfere” with RNA, the precision available with this novel method may allow researchers to make temporary changes to genomes, as opposed to just permanent ones. This new CRISPR system – known as C2c2 – was found to help bacteria protect themselves against viral infection.
“C2c2 opens the door to an entirely new frontier of powerful CRISPR tools,” said Feng Zhang, a senior author of the study, and Core Institute Member of the Broad Institute at the Massachusetts Institute of Technology and the University of Harvard, said in a statement. “There are an immense number of possibilities for C2c2 and we are excited to develop it into a platform for life science research and medicine.”
The multidisciplinary team of researchers were observing the way the bacterium Leptotrichi shahii defends itself against bacteriophages, which are viruses that specifically target bacterial colonies. They infect their hosts by latching on to a series of specific receptors at the surface, before injecting their genetic material – in the form of either DNA or RNA – inside it, which then begins to replicate.
This particular bacterium was discovered to be able to defend itself against RNA bacteriophage attack by using its own in-built CRISPR technique to cleave the incoming RNA strands. The researchers realized that if they could harness this new RNA-snipping technique, it could compliment the widely-used Cas9 DNA editing technique to give bioengineers remarkable genetic modification abilities.
In tests, they were able to use C2c2 to manually target and remove specific RNA sequences, which lowered the ability of the corresponding protein to express itself – a temporary, not permanent change known as a “gene knockdown.”
Ultimately, these knockdowns can be used to change the behavior of an organism without chopping and changing around parts of its DNA genetic sequence; by adding fluorescent tags to RNA segments using C2c2, these temporary alterations can be carefully tracked by researchers or medical professionals.
The only other prominent method that allows gene knockdowns is siRNA, whose precision and range of applications pale in comparison to what C2c2 can manage. Already, one potentially game-changing application of C2c2 has been demonstrated by L. shahii: If this bacterium can use it to defend itself against viral attack, perhaps humans equipped with C2c2 could follow suit.
“C2c2’s greatest impact may be made on our understanding of the role of RNA in disease and cellular function,” added study co-author Omar Abudayyeh, a graduate student in Zhang’s laboratory.
Image in text: A hairpin loop with a section of pre-mRNA, an immature strand of mRNA; the nucleobases are highlighted in green. Vossman/Wikimedia
Synthetic biology can now be used to build organs and could lead to the future creation of cyborgs.
- More than 120,000 people in the U.S. need a life-saving organ transplant, but is synthetic biology the answer?
“What is life?”
Perhaps this is one of the most perennial questions of, well, life. It’s a question further compounded by discoveries that have allowed us to understand what living things are made of and that it’s the exact same material non-living things are made of: molecules.
Then we discovered that what makes living things different from other matter is a special combination of proteins called DNA. This contained everything there was and is (and, to a certain extent, will be) to know about a particular organism. Then, scientists learned how to read the entire DNA sequence (or genome) of organisms 20 years ago, and the possibilities for life took a step forward with the advent of synthetic biology.
Synthetic biology has become the backbone of biotechnology. With advances in the field moving rapidly, we have become capable of more than just reading and editing life. Now, we can, in a manner of speaking, modify or make life into something new. We can build organs that could save the lives of thousands of people in need of organ transplants, and in the future, we could even potentially create cyborgs using the tech.
And with this ability comes so many questions. How far can we go? How far should we go?
MODIFIED MRNA LENGTHENS TELOMERES
MODIFIED MRNA LENGTHENS TELOMERES
Telomeres are protective caps at the ends of chromosomes, which protect DNA during replication. These are shortened and eventually lost over the course of a lifetime, making the cell age and become susceptible to disease. A team of researchers have successfully used altered mRNA to lengthen telomeres in human cells, allowing them to act younger and proliferate more than untreated cells. It is hoped that this could eventually be used to help patients with diseases associated with shortened telomeres, such as Duchenne muscular dystrophy. Helen Blau of Stanford University School of Medicine is senior author of the paper, which was published in the Journal of the Federation of American Societies for Experimental Biology.
At birth, telomeres are roughly 9,000 nucleotides long. Due to the inability of DNA polymerase to begin replication at the end of the chromosome, a bit gets nipped off each time. After a certain number of rounds of mitosis, known as the Hayflick limit, the cell is no longer able to divide. Cells that are required to multiply an incredible number of times, such as stem cells or germ cells in males, freely express a telomere-lengthening enzyme called telomerase in order to keep the cells acting young and healthy. However, it is not generally expressed in adult cells.
“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life,” Blau said in a press release. “This greatly increases the number of cells available for studies such as drug testing or disease modeling.”
The idea of lengthening telomeres is nothing new and has been tried in many ways, though they typically come with various drawbacks. The key to the team’s success was manipulating mRNA to include directions for TERT, an active subunit of telomerase. The effects last for 48 hours, but this transient nature provides an advantage. If TERT became a permanent fixture, and the cell could replicate indefinitely, it increases the risk of developing cancer. Additionally, this method does not cause an immune response, as has been seen by other approaches in the past.
Upon getting treated with the TERT mRNA and receiving more than a 10% increase in telomere length, skin cells were able to replicate 28 more times than their untreated counterparts, while muscle cells replicated three additional times. Moving forward, Blau’s team will be treating other types of cells.
“We’re working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally useful,” Blau said. “One day it may be possible to target muscle stem cells in a patient with Duchenne muscular dystrophy, for example, to extend their telomeres. There are also implications for treating conditions of aging, such as diabetes and heart disease. This has really opened the doors to consider all types of potential uses of this therapy.”
NEW DISCOVERY END AGING
- By observing the transparent cells of roundworms, researchers have uncovered a link between lifespan and the natural cellular process of RNA splicing.
- This research could lead to new breakthroughs in anti-aging treatments that would allow humans to indefinitely keep ourselves healthy, stalling death for as long as possible.
- A new experiment looks into the possibility of replicating stem cell-like conditions through intermittent expressions of genes in order to reverse the signs of aging.
- As a result, human skin cells in a dish looked and behaved young again, and mice with premature aging disease were rejuvenated with a 30% increase in lifespan.
PATTERNS IN SPLICING
Though aging seems like one of the most natural things, an affair common to all living creatures, the process is actually poorly understood by scientists. A new study detailed in Nature aims to shed light on the phenomenon as a research team led by the Harvard T.H. Chan School of Public Health has uncovered a relationship between lifespan and RNA splicing, a core function of cells that allows a single gene to produce a variety of proteins.
The researchers already knew that mutations in RNA splicing could lead to disease, but they wanted to find out if the act of splicing itself had an impact on the aging process. To find out, they designed experimental setups using the roundworm Caenorhabditis elegans, which show visible signs of aging during their short three-week lifespan.
Using fluorescent genetic tools, the team was able to observe the RNA splicing of individual genes in the roundworms’ transparent cells. They noted patterns of splicing that indicated youthfulness or premature aging in the worms and were even able to use these patterns to predict an individual roundworm’s lifespan before any signs of aging became visible. “This…suggests that we might someday be able to use splicing as a kind of biomarker or early signature of aging,” said co-author Caroline Heintz in a press release.
When old age comes, you’ll know it. In addition to telltale signs like greying hair and wrinkled skin though, age comes coupled with an increased risk of age-related diseases. This is why scientists have been studying how aging, which happens on a cellular level, could be halted or even reversed. The latter is the direction researchers at the Salk Institute want to take.
Their research looks into the possibility of replicating stem cell-like conditions through intermittent expressions of genes usually associated with an embryonic state in order to reverse the signs of aging.
“Our study shows that aging may not have to proceed in one single direction,” says senior author Juan Carlos Izpisua Belmonte, Salk Gene Expression Laboratory professor. “It has plasticity and, with careful modulation, aging might be reversed.”
The team’s research is published in the journal Cell.
The researchers prompted cellular rejuvenation through cellular reprogramming that activates the expressions of four genes known as the Yamanaka factors. This process converts cells into induced pluripotent stem cells (iPSCs), — which behave like stem cells, capable of becoming any cell type and can divide indefinitely.
The approach produced promising results: human skin cells in a dish looked and behaved young again, and mice with premature aging disease were rejuvenated with a 30% increase in lifespan.
GETTING IT OUT OF THE LAB
“What we and other stem-cell labs have observed is that when you induce cellular reprogramming, cells look younger,” says Alejandro Ocampo, a research associate and first author of the paper. “The next question was whether we could induce this rejuvenation process in a live animal.”
Of course, iPSCs aren’t necessarily a good thing, especially for adults — after all, non-stop cellular division is a cancer-like behavior and suddenly turning cells young again could result in organ failure.
The team did, however, test the technique on a rare genetic disease called progeria, found in both humans and mice. In the end, they developed a way to induce the Yamanaka factors for a short duration, which was enough to modify the epigenetic marks — which partially drive aging — prematurely dysregulated in progeria.
“[We] now show, for the first time, that by expressing these factors for a short duration you can maintain the cell’s identity while reversing age-associated hallmarks,” said author Pradeep Reddy. The process itself needs to be tested before it can go into actual human trials, and the Salk researchers think it would take about 10 years before it could happen.
IS AGING A DISEASE?
When we shift our view of aging from a natural part of life to something modern medicine can possibly prevent, the next step is finding ways to indefinitely keep ourselves healthy, stalling death for as long as possible.
Other researchers are already looking for ways to stop or at least slow down the biological clock. Researchers at the Stanford School of Medicine used chromosome extensions to increase the rate of cell division, a growth mechanism of our bodies that weakens over time. Another breakthrough is Metformin, the so-called “fountain of youth” drug that began clinical tests in February and can supposedly extend animal life and prevent some cancers.
These developments and Mair’s research on RNA splicing are quite far from explaining exactly why our bodies age, and they’re even farther from significantly stalling the biological clock in humans. Until that happens, the search for a way to extend human life will no doubt continue.