Lifeboat Foundation

Joint research led by Yutaro Shuto, Ryoya Nakagawa, and Osamu Nureki of the University of Tokyo determined the spatial structure of various processes of a novel gene-editing tool called “prime editor.” Functional analysis based on these structures also revealed how a “prime editor” could achieve reverse transcription, synthesizing DNA from RNA, without “cutting” both strands of the double helix. Clarifying these molecular mechanisms contributes greatly to designing gene-editing tools accurate enough for gene therapy treatments. The findings were published in the journal Nature.

The 2020 Nobel Prize in Chemistry was awarded to Jennifer Doudna and Emmanuelle Charpentier for developing a groundbreaking yet simple way to edit DNA, the “blueprint” of living organisms. While their discovery opened new avenues for research, the accuracy of the method and safety concerns about “cutting” both strands of DNA limited its use for gene therapy treatments. As such, research has been underway to develop tools that do not have these drawbacks.

The prime editing system is one such tool, a molecule complex consisting of two components. One component is the prime editor, which combines a SpCas9 protein, used in the first CRISPR-Cas gene editing technology, and a reverse transcriptase, an enzyme that transcribes RNA into DNA. The second component is the prime editing guide RNA (pegRNA), a modified guide RNA that identifies the target sequence within the DNA and encodes the desired edit. In this complex, the prime editor works like a “word processor,” accurately replacing genomic information. The tool has already been successfully implemented in living cells of organisms such as plants, zebrafish, and mice. However, precisely how this molecule complex executes each step of the editing process has not been clear, mostly due to a lack of information on its spatial structure.

Though one in two people will develop some form of cancer in their lifetime, there’s still much we don’t know about this disease. But thanks to continued research efforts, we keep learning more about the biology of cancer. One of these recent discoveries could even transform our understanding of how cancers develop.

But before we talk about the new discovery, let’s first discuss the classical theory that attempts to explain why normal cells become cancer cells. This theory posits that DNA mutations are the primary cause of cancers.

It’s well known that ageing, as well as some lifestyle and environmental factors (such as smoking and UV radiation) cause random DNA mutations (also known as genetic alterations) in our cells. Most genetic alterations trigger cell death or have no consequence.

Duarte et al. report that common genetic variants linked to psychiatric disorders influence the regulation of ancient retroviruses integrated into the genome. This suggests ancient viruses acquired millions of years ago may have shaped modern human brain function.

With advances in genomics research, personalized medicine, and sequencing-based technologies, there is a necessity for purification of high-quality genomic DNA from large volumes of blood. The rapidly growing landscape of biorepositories that store large amounts of DNA from an enormous number of biospecimens further fuels this need to find optimized solutions for reliable purification of DNA. The information derived from the purified DNA is crucial to health science research and facilitates drug discovery, biomarker discovery, clinical implementation projects, etc. For the success of these analyses and to derive relevant information, DNA extraction is the most critical step and must meet the criteria of extraction speed, yield and quality, as well as reproducibility. Many nucleic acid purification kits and automation workflows for processing blood samples in the volume range of 100–250 μL exist, but not many convenient, automated options exist for volumes as high as 2 mL without sample splitting. To fill this opening, Omega Bio-tek has developed a semi-automated solution on the MagBinder^® Fit²⁴ to extract DNA from large volumes of fresh or frozen blood. Here, we provide background information on biobanks, as well as present the solution Omega Bio-tek has developed for DNA extraction from large volumes of whole blood.

A biobank is a specialized repository that systematically collects, processes, stores, and manages biological samples for use in medical research and treatments. The primary purpose of a biobank is to provide a centralized and organized resource of high-quality biological materials, such as blood or tissue, along with relevant clinical and demographic data¹. These invaluable assets are at the center of advancements in cancer treatments, biomarker discovery, and understanding genetic factors for disease. At a high level, biobanks can be classified by two categories¹:

It’s long been assumed that as cells divide in the human body, the genome is faithfully replicated in the resulting daughter cells. While errors are known to arise, there is machinery in the cell that can detect these genetic errors, and can often repair them. When mutations remain in the genome, it raises the risk that disease will arise.

But the human genome is made up of about 6 billion bases, and the human body contains billions, even trillions of cells. And it seems that errors and variations in the genome could actually arise far more often than we knew, according to a new study reported in Nature Genetics that analyzed blood stem cells. The research used advanced sequencing techniques to show that humans are made up of cells whose genomes may be far more heterogeneous that assumed. And these variations between cells are not always small. The research determined that about one out of every forty blood stem cells in healthy people carry major chromosomal alterations in their DNA. These chromosomal changes included copy number variations and rearrangements, but did not seem to cause any deleterious effect.

Sensory hypersensitivity in mice with the Grin2b gene mutation found in patients is related to hyperactivity of the anterior cingulate cortex (ACC) and hyperconnectivity between the ACC and other brain regions. Credit: Institute for Basic Science.

Director Kim Eunjoon states, “This new research demonstrates the involvement of the anterior cingulate cortex (ACC), which has been known for its deep association with cognitive and social functions, in sensory hypersensitivity in autism.”

The hyperactivity of the ACC was also associated with the enhanced functional connectivity between the ACC and other brain areas. It is believed both hyperactivity and the hyperconnectivity of the ACC with various other brain regions are involved with sensory hypersensitivity in Grin2b-mutant mice.

Enhanced neuron growth in the hippocampus, achieved through exercise or genetic methods, aids mice in forgetting strong, maladaptive memories, offering potential for new treatments for PTSD or drug addiction.

Researchers at the University of Toronto, Canada, and Kyushu University, Japan, discovered that enhancing neuron production and subsequently altering neural connections in the hippocampus—through exercise or genetic intervention—enables mice to forget memories associated with trauma or drugs. The findings, reported in the journal Molecular Psychiatry, could offer a new approach to treating mental health conditions like post-traumatic stress disorder (PTSD) or drug addiction.

PTSD is a mental health condition that can be triggered by experiencing or seeing a traumatic event, such as a natural disaster, serious accident, or attack. Worldwide, around 3.9% of the general population has PTSD, with symptoms including vivid flashbacks and avoidance behaviors, such as staying away from places or pushing away people that remind them of the traumatic event.

The human genome is massive, and it contains many highly repetitive sequences that confounded researchers for years. Many of these repeats were simply written off as junk DNA that had no function. However, new research is revealing that many of these regions are much more important than we thought. Some of the repetitive portions of the genome are known to be human endogenous retroviruses (HERVs). These sequences originated from viruses that infected human germ cells millions of years ago and affected our evolution. About eight percent of our genome is thought to be made up of HERVs. These HERVs have also been associated with a variety of psychiatric disorders, although the connection is unclear.

A new study reported in Nature Communications has suggested that HERVs are making a significant but unappreciated contribution to the development of psychiatric disorders, and that they may help explain a genetic component of these disorders that is thought to exist but has not yet been identified.

One tool, called Find My Understudied Genes (FMUG), emerged from a study published in March¹, which first explores why interesting, but relatively under-researched, genes are not highlighted in genetic surveys, and then offers FMUG as a remedy.

The second tool is the Unknome database, created by a team led by Matthew Freeman at the University of Oxford, UK, and Sean Munro at the MRC Laboratory of Molecular Biology, Cambridge, UK, that was described² in 2023.

“We are in the lucky position to know what we don’t know,” says Thomas Stoeger, a biologist at Northwestern University in Chicago, Illinois, and co-author of the FMUG study.