LIN28A

During the fetal stage, a number of so-called cell programs run that are vital to the development of the fetus. Researchers demonstrate that one of these fetal programs appears to protect against acute myeloid leukaemia (AML). During the fetal stage, a number of so-called cell programs run that are vital to the development of the fetus. In a study published in Cell Reports, researchers from Lund University demonstrate that one of these fetal programs appears to protect against acute myeloid leukaemia (AML). "We have used an experimental mouse model that always results in this type of leukaemia. The interesting thing is that, when we to adult mice added a specific molecular cell program that normally only runs during fetal development, over half did not develop AML," says David Bryder, professor of experimental haematology at Lund University. The fetal program that the researchers used consists of the RNA-binding protein LIN28, the normal function of which is to regulate other genes. LIN28 is usually only expressed during fetal development and disappears shortly after birth. "AML is the result of various cell mutations. In our research model, we can follow the development from the first mutation until the disease is established, something that is impossible to do in humans. Our mouses study shows that LIN28 has a strong prophylactic effect," says Mohamed Eldeeb, a doctoral student in Bryder's research group. The researchers first examined samples from a large number of patients diagnosed with AML, 98 per cent of whom turned out to have no expression of LIN28 whatsoever. In those who did, the level was very low. To understand more about what happens when LIN28 is activated, the researchers then carried out more in-depth molecular and functional studies using their animal model. "We could see that, in mice, the molecular fetal cell program protected against disease by colliding with the mechanism that drives AML, which might explain why leukaemia is rare in newborns. Given the robust effect we have demonstrated, it will be interesting to study whether the fetal cell program can be used to prevent disease later in life. That said, one should be aware that it remains to be seen how we can reactive such a program in human cells," says Bryder.

BOSTON, Sept. 08, 2022 (GLOBE NEWSWIRE) -- TransCode Therapeutics, Inc. (Nasdaq: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, today announced the appointment of Frank J. Slack, PhD, to its advisory board. “Dr. Slack is one of the most preeminent scientists in the field of small noncoding RNA,” commented Zdravka Medarova, PhD, Co-Founder and CTO of TransCode. “Having pioneered pivotal studies proving that microRNAs drive oncogenesis and represent critical targets for the treatment of cancer, his guidance will prove indispensable as TransCode enters the clinical phase of development.” Dr. Slack is the Shields Warren Mallinckrodt Professor, Department of Pathology, and Director of the Harvard Medical School Initiative for RNA Medicine (HIRM), Beth Israel Deaconess Medical Center. Directed by Dr. Slack, the HIRM Initiative harnesses the potential of RNA to revolutionize the way cancer and other diseases are treated and diagnosed. “We are excited to welcome Dr. Slack to our advisory board,” commented Michael Dudley, President and Chief Executive Officer of TransCode. “With final preparations underway to begin our first in-human studies with our lead candidate, TTX-MC138, Dr. Slack’s tremendous depth of experience in microRNA bolsters our team at an ideal time as we move into the next stage of development.” Dr. Slack received his BSc from the University of Cape Town in South Africa before completing his PhD in molecular biology at Tufts University School of Medicine. He began work on microRNAs as a postdoctoral fellow in Gary Ruvkun’s laboratory at Harvard Medical School, where he co-discovered the first human microRNA, let-7. Dr. Slack’s laboratory is at the forefront of the small RNA revolution. In addition to co-discovering let-7 and showing that it is a tumor suppressor that controls key cancer genes such as RAS, MYC and LIN28, the Slack lab also proved that microRNAs act as key oncogenes and developed strategies to target these oncomiRs for cancer therapy. Their research also extends to discovery of additional small RNAs in cancer, aging and diabetes as well as identifying novel SNPs in the non-coding portions of the genome with an eye to identifying the next generation of actionable targets in cancer. About TransCode Therapeutics TransCode is an RNA oncology company created on the belief that cancer can be effectively treated using RNA therapeutics. The Company has created a platform of drug candidates designed to target a variety of tumor types with the objective of significantly improving patient outcomes. The Company’s lead therapeutic candidate, TTX-MC138, is focused on treating metastatic cancer, which is believed to cause approximately 90% of all cancer deaths totaling over nine million per year worldwide. The Company believes that TTX-MC138 has the potential to produce regression without recurrence in a range of cancers, including breast, pancreatic, ovarian and colon cancer, glioblastomas and others. Two of the Company’s other drug candidates, TTX-siPDL1 and TTX-siLIN28B, focus on treating tumors by targeting PD-L1 and LIN28B, respectively. TransCode also has three cancer-agnostic programs—TTX-RIGA, an RNA–based agonist of the retinoic acid-inducible gene I, or RIG-I, approach designed to drive an immune response in the tumor microenvironment; TTX-CRISPR, a CRISPR/Cas9–based therapy platform for the repair or elimination of cancer-causing genes inside tumor cells; and TTX-mRNA, an mRNA-based platform for the development of cancer vaccines designed to activate cytotoxic immune responses against tumor cells. Forward-Looking Statements This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, without limitation, statements concerning TransCode’s management and advisory board, statements concerning the results of RNA research, statements concerning the potential for treating cancer with RNA therapeutics, statements concerning the timing and outcome of expected regulatory filings and clinical trials, including the filing of an eIND for the planned first-in-human study of TTX-MC138, statements concerning the timing and outcome of this study, including whether this study will demonstrate proof-of-mechanism, statements concerning patent applications, and statements concerning TransCode’s development programs and TTX technology platform generally. Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the risk associated with drug discovery and development; the risk that the results of our planned clinical trials will not be consistent with our pre-clinical studies or expectations; risks associated with the timing and outcome of TransCode’s planned regulatory submissions; risks associated with TransCode’s planned clinical trials for its product candidates; risks associated with obtaining, maintaining and protecting intellectual property; risks associated with TransCode’s ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties; the risk of competition from other companies developing products for similar uses; risks associated with TransCode’s financial condition and its need to obtain additional funding to support its business activities, including TransCode’s ability to continue as a going concern; risks associated with TransCode’s dependence on third parties; and risks associated with the COVID-19 coronavirus. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause TransCode’s actual results to differ from those contained in or implied by the forward-looking statements, see the section entitled “Risk Factors” in TransCode’s Annual Report on Form 10-K for the year ended December 31, 2021, as well as discussions of potential risks, uncertainties and other important factors in any subsequent TransCode filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release; TransCode undertakes no duty to update this information unless required by law. For more information, please contact: TransCode Therapeutics, Inc.Alan Freidman, VP Investor Relationsalan.freidman@transcodetherapeutics.com Dave Gentry, CEORedChip CompaniesOffice: 1.800.RED.CHIP (733.2447)Cell: 407.491.4498RNAZ@redchip.com