An iterative engineering approach to improve prime editor delivery helped scientists correct genetic vision defects in mice.
A new study, funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, describes a promising way to carry genetic material into the brain to reach cellular targets.
A new open-access RNA sequencing dataset, MAGE, of 731 individuals across geographically diverse human populations provides a valuable resource to study genetic diversity and evolution and expands the capacity to identify new genetic associations.
It’s no revelation that the human body undergoes natural wear and tear as we age. But you might be surprised to discover that this process isn’t as gradual as we’d presumed.
A recent study reveals some remarkable truths about aging, specifically when and how our bodies start to ‘break down’
The man at the helm of the study is Michael Snyder. Chair of genetics at Stanford School of Medicine and recognized for his exceptional contribution to the field, his team’s research provides some fascinating insights into the specifics of our biological aging process.
Bacteria defend themselves from viral infection using diverse immune systems, many of which sense and target foreign nucleic acids. Defense-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this immune strategy by instead leveraging DNA synthesis, but the identities and functions of their DNA products remain largely unknown. Here we show that DRT2 systems execute an unprecedented immunity mechanism that involves de novo gene synthesis via rolling-circle reverse transcription of a non-coding RNA (ncRNA). Unbiased profiling of RT-associated RNA and DNA ligands in DRT2-expressing cells revealed that reverse transcription generates concatenated cDNA repeats through programmed template jumping on the ncRNA. The presence of phage then triggers second-strand cDNA synthesis, leading to the production of long double-stranded DNA. Remarkably, this DNA product is efficiently transcribed, generating messenger RNAs that encode a stop codon-less, never-ending ORF (neo) whose translation causes potent growth arrest. Phylogenetic analyses and screening of diverse DRT2 homologs further revealed broad conservation of rolling-circle reverse transcription and Neo protein function. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation, and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA.
One-Sentence Summary Bacterial reverse transcriptases synthesize extrachromosomal genes via rolling-circle amplification to confer potent antiviral immunity.
Columbia University has filed a patent application related to this work. S.H.S. is a co-founder and scientific advisor to Dahlia Biosciences, a scientific advisor to CrisprBits and Prime Medicine, and an equity holder in Dahlia Biosciences and CrisprBits.
In the quest to unravel the complexities of neural circuits, scientists are beginning to use genetically encoded voltage indicators (GEVIs) to visualize electrical activity in the brain. These indicators are crucial for understanding how neurons communicate and process information. However, the effectiveness of one-photon (1P) versus two-photon (2P) voltage imaging has remained a topic of debate. A recent study by researchers at Harvard University sheds light on the relative merits and limitations of these two imaging techniques, providing valuable insights for the scientific community.
DNA, or deoxyribonucleic acid, is the molecular system responsible for carrying genetic information in living organisms, utilizing its two helical strands to transcribe and amplify this information. Scientists are highly interested in developing artificial molecular systems that can match or even exceed the functionality of DNA. Double-helical foldamers represent one such promising molecular system.
Helical foldamers are a class of artificial molecules that fold into well-defined helical structures like helices found in proteins and nucleic acids. They have garnered considerable attention as stimuli-responsive switchable molecules, tuneable chiral materials, and cooperative supramolecular systems due to their chiral and conformational switching properties.
Double-helical foldamers exhibit not only even stronger chiral properties but also unique properties, such as the transcription of chiral information from one chiral strand to another without chiral properties, enabling potential applications in higher-order structural control related to replication, like nucleic acids. However, the artificial control of the chiral switching properties of such artificial molecules remains challenging due to the difficulty in balancing the dynamic properties required for switching and stability. Although various helical molecules have been developed in the past, reversal of twist direction in double-helix molecules and supramolecules has rarely been reported.
Columbia researchers discovered that bacteria can create free-floating, temporary genes outside their chromosomes, challenging the long-held belief that all genetic instructions are contained within the genome. This finding opens the possibility that similar genes could exist in humans, potentially revolutionizing our understanding of genetics and gene editing.
Since the genetic code was first deciphered in the 1960s, our genes have appeared like an open book. By interpreting our chromosomes as linear sequences of letters, akin to sentences in a novel, we can identify the genes within our genome and understand how changes in a gene’s code influence health.
This linear rule of life was thought to govern all forms of life—from humans down to bacteria.
Researchers at the University of Maryland genetically modified poplar trees to produce high-performance, structural wood without the use of chemicals or energy-intensive processing. Made from traditional wood, engineered wood is often seen as a renewable replacement for traditional building materials like steel, cement, glass and plastic. It also has the potential to store carbon for a longer time than traditional wood because it can resist deterioration, making it useful in efforts to reduce carbon emissions.
But the hurdle to true sustainability in engineered wood is that it requires processing with volatile chemicals and a significant amount of energy, and produces considerable waste. The researchers edited one gene in live poplar trees, which then grew wood ready for engineering without processing.
The research was published online on August 12, 2024, in the Journal Matter.
Aging is the major risk factor for the development of chronic diseases such as cardiovascular disease, cancer, diabetes, and dementia. Therefore, drugs that slow the aging process may help extend both lifespan and healthspan (the length of time that people are healthy).
In a study published online on February 29 in Medical Research Archives, Albert Einstein College of Medicine researchers evaluated U.S. Food and Drug Administration-approved drugs for their anti-aging potential. In ranking those drugs, they gave equal weight to preclinical studies (i.e., effect on rodent lifespan and healthspan) and clinical studies (i.e., reduced mortality from diseases the drugs were not intended to treat). The four therapeutics judged most promising for targeting aging were SGLT2 inhibitors, metformin, bisphosphonates, and GLP-1 receptor agonists. Since these drugs have been approved for safety and used extensively, the researchers recommend they be evaluated for their anti-aging potential in large-scale clinical trials.
The study’s corresponding author was Nir Barzilai, M.D., director of Einstein’s Institute for Aging Research, professor of medicine and of genetics and the Ingeborg and Ira Leon Rennert Chair in Aging Research at Einstein, and a member of the National Cancer Institute–designated Montefiore Einstein Comprehensive Cancer Center. The lead author was Michael Leone, a medical student at Einstein.
Bacteria defend themselves from viral infection using diverse immune systems, many of which sense and target foreign nucleic acids. Defense-associated reverse transcriptase (DRT) systems provide an intriguing counterpoint to this immune strategy by instead leveraging DNA synthesis, but the identities and functions of their DNA products remain largely unknown. Here we show that DRT2 systems execute an unprecedented immunity mechanism that involves de novo gene synthesis via rolling-circle reverse transcription of a non-coding RNA (ncRNA). Unbiased profiling of RT-associated RNA and DNA ligands in DRT2-expressing cells revealed that reverse transcription generates concatenated cDNA repeats through programmed template jumping on the ncRNA. The presence of phage then triggers second-strand cDNA synthesis, leading to the production of long double-stranded DNA. Remarkably, this DNA product is efficiently transcribed, generating messenger RNAs that encode a stop codon-less, never-ending ORF (neo) whose translation causes potent growth arrest. Phylogenetic analyses and screening of diverse DRT2 homologs further revealed broad conservation of rolling-circle reverse transcription and Neo protein function. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation, and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA.
