KLF4

TOULOUSE, France & PARIS--( BUSINESS WIRE )--Flash Therapeutics, a French CDMO specialized in the bioproduction of viral vectors for the transfer of genetic material, is extremely proud to count the CEA, in particular, l’Institut de biologie François Jacob - Laboratoire de Génomique et Radiobiologie de la Kératinopoïèse – LGRK , among its major customers. Thanks to the quality of Flash Therapeutics' vectors, the LGRK has been sourcing specific products from our company for over 10 years to support its research activities, in particular, to study the intrinsic properties and regenerative capacity of skin stem cells. The CEA has published an excellent article on epidermal stem cells entitled " KLF4 inhibition promotes the expansion of keratinocyte precursors from adult human skin and of embryonic-stem-cell-derived keratinocytes " in Nature Biomed Engineering by Nicolas Fortunel & al. Flash Therapeutics and the CEA's Institut de biologie François Jacob are currently discussing expanding their partnership, given their complementary nature. Jérôme Bédier , CEO of Flash Therapeutics: "We are delighted to be partnering with the CEA, the leading French and European player in the field of energy and technology. This approach builds on more than 10 years of collaboration and is in line with Flash's key mission: to discover and bring forward innovative technologies for highly effective therapies on a commercial scale ". About Flash Therapeutics: Founded in 2005 and based at the Oncopole site in Toulouse, Flash Therapeutics is a CDMO specialized in the industrial bioproduction of DNA and RNA vectors to cover a wide range of applications in gene and cell therapy and vaccines. Thanks to its robust platform and manufacturing process, Flash Therapeutics delivers high-purity, high-concentration viral vectors for research, pre-clinical, clinical and commercial phases. About the CEA: The CEA's role is to inform public decision-making by providing scientific and technological solutions to the driving forces (companies, local authorities), to better manage major societal changes: energy transition, digital, healthcare of the future, global defence and security. Its 21,000 employees work at the heart of 9 centres equipped with major research infrastructures, as part of academic and industrial partnerships in France, Europe and internationally.

Scientists have discovered the role of microRNA on inflammation in lupus disease. They identified the microRNAs that are downregulated in the disease and how they converge to cause the disease. A group of researchers from the Graduate School of Medicine at Nagoya University in Japan have discovered the impact of microRNA (miRNA) on inflammation in lupus in mice. They identified two miRNAs that are downregulated in the disease and an uncommon situation that occurs in which multiple miRNAs regulate the same set of genes. Although the human body has many types of RNA, the most important is messenger RNA, which is involved in the creation of proteins in the body. The body also contains miRNA, which binds to regions of the messenger RNA to inhibit protein production and regulate several important bodily functions such as development, growth, and metabolism. Problems with miRNA are associated with several diseases including cancer and HIV. Now, the Nagoya University research group has identified the role of miRNA in systemic lupus erythematosus, a disease in which the human immune system attacks itself. They published their findings in BMC Biology. Pairing with the correct messenger RNA target is determined by the 'seed' of miRNA, a sequence that determines whether the miRNA can bind or not. The seed is like a 'key' to the messenger RNA's 'lock.' However, this is complicated by the nature of miRNA's interaction with messenger RNA as a single particle of messenger RNA may be regulated by multiple miRNAs and the miRNA-messenger RNA pairs do not have to be an exact match to exert an effect. As the effects of a single miRNA on a binding receptor site tend to be modest, stronger effects are often regulated by multiple miRNAs working in concert. This occurs through two processes. The first of these processes is 'neighborhood' miRNA co-targeting, where two nearby miRNAs affect messenger RNA. The second, is 'seed overlap' miRNA co-targeting, which is similar to the neighborhood type except both have similar nucleotides, so they bind to messenger RNA in such a way that some of their nucleotides overlap. Given that altered miRNA expression has been reported in lupus disease, researchers have long suspected a connection. Now, a group of scientists, headed by Professor Hiroshi Suzuki at the Department of Molecular Oncology, and Lecturer Noritoshi Kato and Researcher Hiroki Kitai at the Department of Nephrology at the Nagoya University Graduate School of Medicine, have performed miRNA expression profiling using mice with lupus to investigate the role of miRNA in the disease. The researchers found that two microRNAs, miR-128 and miR-148a, were down-regulated in plasmacytoid dendritic cells in lupus patients. As plasmacytoid dendritic cells play a crucial role in antiviral immunity and antibody production, they have been implicated in the initiation and development of several autoimmune and inflammatory diseases, including lupus. Both miR-128 and miR-148a target a gene called KLF4, which is associated with inflammatory control and the production of cytokines that regulate the activity of the immune system. "Assuming that the expression levels of the other miRNA are maintained, the downregulation of one miRNA can be compensated for by the other microRNA," Suzuki explains. "However, when two miRNAs decrease simultaneously, as in lupus disease, alterations in their target -- in this case KLF4 -- emerge." One of the most important findings of the study was that as miR-128 and miR-148a share common nucleotides, they can bind to messenger RNA using 'seed overlap' miRNA co-targeting. "miR-128 and miR-148a target KLF4 through extensive 'seed overlap' miRNA cotargeting. In this case, it negatively regulates the production of inflammatory cytokines," says Suzuki. "Therefore, this study collectively suggests the complexity of different modes of miRNA cotargeting and the importance of their perturbations in human diseases." The researchers also performed integrative analyses, discovering that "seed overlap" miRNA cotargeting of KLF4 is a prevalent feature in other species. "We found that the conserved overlap site of KLF4 is the same in most species between humans and Coelacanths," said Suzuki. "Therefore, we expanded these findings by integratively analyzing seed overlap patterns of all miRNAs and the conservation patterns of 'seed overlap' target sites." Suzuki and the research team discovered two main conservation classes of miRNA target sites. The first was shared by eutherian mammals, including animals that have a placenta. The second was shared by other animals, including humans and Coelacanths, and has a stronger association with both "seed overlap" and "neighborhood" miRNA cotargeting. "Our study provides a comprehensive view of 'seed overlap' miRNA cotargeting, which is very important for the process by which lupus develops from the viewpoint of gene regulation and miRNA evolution. These findings highlight the importance of miRNA co-targeting in human pathology and the unique evolutionary aspects of miRNA co-targeting and miRNA target site conservation," Suzuki explains. Suzuki also sees the potential of his research in treating lupus patients: "Testing for downregulation of the two miRNAs may help identify patients with high level of inflammation who may benefit from specific therapeutic development," he says.

SAN DIEGO--(BUSINESS WIRE)-- Rejuvenate Bio, today announced new preclinical research published to the preprint server bioRxiv, that evaluates how partial reprogramming could be a potential treatment in the elderly to reverse age-associated diseases and potentially extend human lifespan. Aging is best defined as the chronic dysregulation of gene expression networks over time leading to subsequent deteriorated tissue and organ function causing age-related functional decline and diseases. Recent studies have demonstrated that partial reprogramming using Yamanaka factors can reverse age-related changes in cellulo and in vivo, including extending the lifespan of progeroid mice. A subset of factors (OCT4, SOX2, and KLF4; OSK) have been used to reverse damage to the optic nerve. However, to date, whether OSK is sufficient for partial reprogramming of cells and to extend the lifespan of aged wild type mice is unknown. The study showed that a doxycycline inducible 2-part adeno-associated virus (AAV) system is able to deliver and express OSK in 124 week old mice and have systemic effects that enhance health parameters and increase remaining lifespan by 70% over controls. The study also observed epigenetic patterns consistent with age reversal in methylation studies of liver and heart tissue from treated mice relative to untreated controls. "The main causes of death in the elderly are age-related diseases, such as heart disease, stroke, and specific cancers,” said Noah Davidsohn, Ph.D., Chief Scientific Officer and Co-Founder, Rejuvenate Bio. “While aging cannot currently be prevented, its impact on life and healthspan can potentially be minimized by interventions that aim to return gene expression networks to optimal function. The study results suggest that partial reprogramming could be a potential treatment in the elderly for reversing age-associated diseases and could extend human lifespan.” About Rejuvenate Bio Rejuvenate Bio is a spinout from the Wyss Institute at Harvard focused on reversing aging and eliminating age-related disease. Rejuvenate Bio utilizes gene therapy, proprietary targets, and tools to bring treatments to patients suffering from age-related conditions. The company is developing a pipeline of therapies with applications in cardiac and metabolic disease. The company raised a Series A financing in 2021 led by Kendall Capital Partners, Digitalis Ventures, KdT Ventures and V Capital. Rejuvenate Bio is based in San Diego for more information, visit .