KLF4

Data replicate and expand upon the potential of ER-100 to improve retinal ganglion cell function and restore visual function in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (NAION)BOSTON, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Life Biosciences (“Life Bio”), a biotechnology company advancing innovative cellular rejuvenation technologies to reverse diseases of aging and injury and ultimately restore health for patients, today announced new data presented at the 2024 American Association of Ophthalmology (AAO) Annual Meeting that took place in Chicago, Illinois from October 18-21, 2024. Results replicate previously reported nonhuman primate (NHP) data and further expand our knowledge on dosing and timing of treatment. ER-100, a novel partial epigenetic reprogramming gene therapy containing Oct-4, Sox-2 and Klf-4 (OSK), was administered via a single intravitreal injection along with daily systemic doxycycline to NHPs with a NAION-like injury. Immunohistochemistry confirmed expression of each transcription factor (Oct-4, Sox-2 and Klf-4) in discrete cells in the perifoveal regions in ER-100 treated NHPs relative to vehicle. Furthermore, ER-100 significantly reduced deficits in pattern electroretinogram and axon density measures when administered in both prevention and rescue paradigms. Collectively, these results demonstrate that ER-100 successfully targets retinal ganglion cells and reduces the loss of visual function in an NHP model of NAION. Life Bio remains on track to initiate the first human clinical study evaluating ER-100 for optic neuropathies in the second half of 2025. “Partial epigenetic reprogramming has the potential to restore visual function for those with optic neuropathies such as NAION and glaucoma,” said Sharon Rosenzweig-Lipson, Ph.D., Chief Scientific Officer of Life Bio. “The data shared today replicate and build upon our understanding of the dosing of ER-100 and the timing of the treatment window relative to the onset of NAION-related damage. We look forward to advancing this program toward human clinical trials next year for patients affected by these age-related optic neuropathies.” About Life Biosciences Life Biosciences is a biotechnology company advancing innovative cellular rejuvenation platforms to reverse diseases of aging and injury and ultimately restore health for patients. The company is focusing on two platforms targeting key mechanisms underlying aging biology, epigenetic reprogramming and chaperone-mediated autophagy, to restore cells to a more youthful state. Therapies developed within these platforms have the potential to prevent, treat, and/or reverse multiple aging-related diseases. For more information, please visit www.lifebiosciences.com or follow us on Twitter and LinkedIn. Media Contact Kristin Politi, Ph.D.LifeSci Communicationskpoliti@lifescicomms.com(646) 876-4783

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.