Today, we chronicle the progress of partial cellular reprogramming and discuss how this powerful treatment may be able to reprogram cells back into a youthful state, at least partially reversing epigenetic alterations, one of the proposed reasons we age.
For those of you new to the subject of epigenetic alterations you can learn more by clicking on the topic box below, for the more seasoned readers, feel free to skip ahead.
Gene editing has shown great promise as a non-heritable way to treat a wide range of conditions, including many genetic diseases and more recently, even COVID-19. But could a version of the CRISPR gene-editing tool also help deliver long-lasting pain relief without the risk of addiction associated with prescription opioid drugs?
In work recently published in the journal Science Translational Medicine, researchers demonstrated in mice that a modified version of the CRISPR system can be used to “turn off” a gene in critical neurons to block the transmission of pain signals [1]. While much more study is needed and the approach is still far from being tested in people, the findings suggest that this new CRISPR-based strategy could form the basis for a whole new way to manage chronic pain.
This novel approach to treating chronic pain occurred to Ana Moreno, the study’s first author, when she was a Ph.D. student in the NIH-supported lab of Prashant Mali, University of California, San Diego. Mali had been studying a wide range of novel gene-and cell-based therapeutics. While reading up on both, Moreno landed on a paper about a mutation in a gene that encodes a pain-enhancing protein in spinal neurons called NaV1.7.
“The axons of nerve cells function a bit like a railway system, where the cargo is essential components required for the cells to survive and function. In neurodegenerative diseases, this railway system can get damaged or blocked,” Tasneem Khatib, the study’s first author, explained in a statement. “We reckoned that replacing two molecules that we know work effectively together would help to repair this transport network more effectively than delivering either one alone, and that is exactly what we found.”
Most neurodegenerative diseases are caused by multiple genetic abnormalities, making them difficult to address with gene therapy targeted at single mutations. Astellas is working on a gene therapy that expresses two proteins, and a University of Cambridge team has shown that it holds promise in glau…
UC scientists and physicians hope to permanently cure patients of sickle cell disease by using CRISPR-Cas9 to replace a defective gene with the normal version.
In 2014, two years after her Nobel Prize-winning invention of CRISPR-Cas9 genome editing, Jennifer Doudna thought the technology was mature enough to tackle a cure for a devastating hereditary disorder, sickle cell disease, that afflicts millions of people around the world, most of them of African descent. Some 100000 Black people in the U.S. are afflicted with the disease.
Mobilizing colleagues in the then-new Innovative Genome Institute (IGI) — a joint research collaboration between the University of California, Berkeley, and UC San Francisco — they sought to repair the single mutation that makes red blood cells warp and clog arteries, causing excruciating pain and often death. Available treatments today typically involve regular transfusions, though bone marrow transplants can cure those who can find a matched donor.
After six years of work, that experimental treatment has now been approved for clinical trials by the U.S. Food and Drug Administration, enabling the first tests in humans of a CRISPR-based therapy to directly correct the mutation in the beta-globin gene responsible for sickle cell disease. Beta-globin is one of the proteins in the hemoglobin complex responsible for carrying oxygen throughout the body.
Researchers in Australia have discovered a gene responsible for a particularly aggressive type of hormone-sensitive breast cancer which has tragically low survival rates.
“Hopefully this will dramatically improve the poor outcomes these patients currently suffer,” said Harry Perkins Institute of Medical Research epigeneticist Pilar Blancafort.
It’s hard to overstate just how different cancers can be from one another. Even under the umbrella of ‘breast cancer’ lie several types, such as hormone receptor sensitive, HER2 positive, or non-hormone sensitive breast cancer; within those groups, there are even more types that can respond to treatments differently from one another.
Experiments with this antibody revealed that BMP signaling is essential for determining the number of teeth in mice. Moreover, a single administration was enough to generate a whole tooth.
Japan — The tooth fairy is a welcome guest for any child who has lost a tooth. Not only will the fairy leave a small gift under the pillow, but the child can be assured of a new tooth in a few months. The same cannot be said of adults who have lost their teeth.
A new study by scientists at Kyoto University and the University of Fukui, however, may offer some hope. The team reports that an antibody for one gene — uterine sensitization associated gene-1 or USAG-1 — can stimulate tooth growth in mice suffering from tooth agenesis, a congenital condition. The paper was published in Science Advances.
Although the normal adult mouth has 32 teeth, about 1% of the population has more or fewer due to congenital conditions. Scientists have explored the genetic causes for cases having too many teeth as clues for regenerating teeth in adults.
Stanford University neurobiologist Sergiu Pașca has been making brain organoids for about 10 years, and his team has learned that some of these tissue blobs can thrive in a dish for years. In the new study, they teamed up with neurogeneticist Daniel Geschwind and colleagues at the University of California, Los Angeles (UCLA), to analyze how the blobs changed over their life spans…
…They noticed that when an organoid reached 250 to 300 days old—roughly 9 months—its gene expression shifted to more closely resemble that of cells from human brains soon after birth. The cells’ patterns of methylation—chemical tags that can affix to DNA and influence gene activity—also corresponded to increasingly mature human brain cells as the organoids aged, the team reports today in Nature Neuroscience.
Organoids develop genetic signatures of postnatal brains, possibly broadening their use as disease models.
Sleep deprivation causes an inflammatory response that results in negative health outcomes.
Summary: Study sheds light on DNA methylation related to sleep deprivation in those with shift-work disorder.
Source: University of Helsinki
Long-term sleep deprivation is detrimental to health, increasing the risk of psychiatric and somatic disorders, such as depression and cardiovascular diseases. And yet, little is known about the molecular biological mechanisms set in motion by sleep deprivation which underlie related adverse health effects.
In a recently published study, the University of Helsinki, the Finnish Institute for Health and Welfare, the Finnish Institute of Occupational Health and the Finnair airline investigated dynamic changes to DNA methylation in shift workers. DNA methylation denotes epigenetic regulation that modifies gene function and regulates gene activity without changing the sequence of bases in the DNA.
Researchers can now control the order in which CAS9 makes edits to cell DNA instead of performing all edits at once.
Researchers from the University of Illinois Chicago have discovered a new gene-editing technique that allows for the programming of sequential cuts—or edits—over time.
CRISPR is a gene-editing tool that allows scientists to change the DNA sequences in cells and sometimes add a desired sequence or genes. CRISPR uses an enzyme called Cas9 that acts like scissors to make a cut precisely at a desired location in the DNA. Once a cut is made, the ways in which cells repair the DNA break can be influenced to result in different changes or edits to the DNA sequence.
The discovery of the gene-editing capabilities of the CRISPR system was described in the early 2010s. In only a few years, scientists became enamored with the ease of guiding CRISPR to target almost any DNA sequence in a cell or to target many different sites in a cell in a single experiment.
The genome editing technology CRISPR has emerged as a powerful new tool that can change the way we treat disease. The challenge when altering the genetics of our cells, however, is how to do it safely, effectively, and specifically targeted to the gene, tissue and organ that needs treatment. Scientists at Tufts University and the Broad Institute of Harvard and MIT have developed unique nanoparticles comprised of lipids—fat molecules—that can package and deliver gene editing machinery specifically to the liver. In a study published today in the Proceedings of the National Academy of Sciences, they have shown that they can use the lipid nanoparticles (LNPs) to efficiently deliver the CRISPR machinery into the liver of mice, resulting in specific genome editing and the reduction of blood cholesterol levels by as much as 57%—a reduction that can last for at least several months with just one shot.
The problem of high cholesterol plagues more than 29 million Americans, according to the Centers for Disease Control and Prevention. The condition is complex and can originate from multiple genes as well as nutritional and lifestyle choices, so it is not easy to treat. The Tufts and Broad researchers, however, have modified one gene that could provide a protective effect against elevated cholesterol if it can be shut down by gene editing.
The gene that the researchers focused on codes for the angiopoietin-like 3 enzyme (Angptl3). That enzyme tamps down the activity of other enzymes—lipases—that help break down cholesterol. If researchers can knock out the Angptl3 gene, they can let the lipases do their work and reduce levels of cholesterol in the blood. It turns out that some lucky people have a natural mutation in their Angptl3 gene, leading to consistently low levels of triglycerides and low-density lipoprotein (LDL) cholesterol, commonly called “bad” cholesterol, in their bloodstream without any known clinical downsides.
