Latest news with #ADAR1
Yahoo
11-06-2025
- Science
- Yahoo
Kanazawa University research: High-speed AFM and 3D modelling help towards understanding the dynamics of a protein implicated in several cancers
KANAZAWA, Japan, June 11, 2025 /PRNewswire/ -- Researchers at the Nano Life Science Institute (WPI-NanoLSI), Kanazawa University observe and model how the enzyme ADAR1 interacts with double-stranded RNA, which may be useful for future cancer treatment strategies. An enzyme type noted in several cancers is the family of adenosine deaminases acting on RNA (ADARs). These enzymes convert adenosines in double-stranded RNA (dsRNA) into inosines, which cells read as guanosines. As such, ADARs can contribute to changes in protein-coding sequences and diminish the robustness of various RNA processes. Studies have shown that silencing one type of ADAR – ADAR1 – can prevent cancer proliferation and sensitize cancers to immunotherapy, suggesting that they could be a promising target for cancer treatments. However, so far, it has been difficult to pin down information on the structural dynamics of ADAR1 due to its size and complexity. Now, researchers led by Madhu Biyani at Kanazawa University, WPI-NanoLSI, Yasuhiro Isogai at Toyama Prefectural University, and Manish Biyani at Ishikawa Create Labo and Kwansei Gakuin University have combined high-speed atomic force microscopy (HS-AFM) and 3D modelling to shed light on the enzyme's conformations and interactions with dsRNA. Like many proteins, ADAR1 functions through changes in its conformation. However, most experimental techniques for determining protein structure, as well as 3D modelling algorithms, give static or average conformations that obscure the structural dynamics so important to the protein's function. Combining 3D modelling with HS-AFM proved helpful in shedding light on these dynamic aspects of ADAR1. The researchers first used 3D modelling based on the machine learning algorithm AlphaFold2 to predict the conformations of the enzyme and noted that it could take the form of monomers, dimers, trimers, and tetramers. HS AFM observations, as well as theoretically simulated HS AFM, supported these initial conclusions regarding the possible oligomer formations. The researchers then looked at the conformations the enzyme formed in the presence of double-stranded RNA (dsRNA). In particular, the researchers focused on a certain aryl hydrocarbon receptor 3'UTR mRNA as the target for ADAR1, since this receptor is known to be involved in the metabolism of substances alien to the body at those points. Observations of the dsRNA with HS-AFM not only agreed with previous structural studies but were able to provide insights into the structure of the target region in particular. Thanks to the speed and resolution of the HS-AFM image capture, the researchers were able to identify different conformations in the proteins that seemed to relate to distinct phases of the deaminizing process. In their report of the work, the researchers explain how ADAR1 first "searches" for the dsRNA and on "recognizing" it, adopts a flexible conformation as it approaches. The enzyme then engages in what the researchers describe as "capture" of the dsRNA backbone, for which the conformation transitions to something more stable and "anchor-like". The researchers highlight the role of dsRNA binding domains (dsRBDs) to stabilize the interaction with the dsRNA at this stage. They also note "a visibly large interfacial interaction between the deaminase domains, forming a dimer" as the enzyme dimer loops out on the dsRNA. The enzyme subsequently scans the RNA and dissociates to search for adenosine sites to convert. "These observations suggest that the dsRBDs are critical for initiating interactions between the deaminase domains, thereby promoting the formation of a stable, functional dimeric complex capable of efficiently binding and catalyzing the editing of dsRNA substrates," the researchers conclude in their report, thereby flagging the insights this study offers for further work towards possible cancer therapeutics. The researchers further propose future studies to compare ADAR1 and ADAR2, and to perform mutation analyses to clarify how ADAR1 dimerization influences A-to-I RNA editing, ultimately aiming to develop effective ADAR1 inhibitors. Figure 1: Three-dimensional modeling analysis of ADAR1 2025 Biyani, et al., Nature Communications Figure 2: Simulated AFM images of ADAR1 2025 Biyani, et al., Nature Communications Glossary Atomic force microscopy This imaging technique uses a nanosized tip at the end of a cantilever that is scanned over a sample. It can be used to determine the topography of a sample surface from the change in the strength of forces between the tip and the sample with distance, and the resulting deflection of the cantilever. It was first developed in the 1980s, but a number of modifications have augmented the functionality of the technique since. It is better suited to imaging biological samples than the scanning tunnelling microscope that had been previously developed because it does not require a conducting sample. In the 2000s, Toshio Ando at Kanazawa University was able to improve the scanning speed to such an extent that moving images could be captured. This allowed people to use the technique to visualize dynamic molecular processes for the first time. ADARs Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine, which is interpreted by cells as guanosine. This editing can influence alternative splicing, miRNA processing, double-stranded RNA stability, and protein-coding sequences. In mammals, there are two known ADARs responsible for adenosine to inosine RNA editing – ADAR1 and ADAR2. Notably, overexpression and increased activity of ADAR1 have been observed in cancers of the liver, breast, esophagus, prostate, and bone marrow. 3D modelling Several techniques are now available for protein structure prediction. In this study, the researchers used AlphaFold2 to model the structure of human ADAR1. Due to disorder regions in the N-terminal 822 residues, the final model focused on residues 823-1226, which encompass the deaminase domain. This monomer model served as the basis for building higher-order structures—dimer, trimer, tetramer, and polymer by superimposing it onto the ADAR2 dimer structure (PDB ID:1ZY7) through sequence alignment. Since determining ADAR1's full structure is challenging due to its size and complexity, the better-characterized ADAR2 provided a template to generate ADAR1 multimer models. Reference Madhu Biyani, Yasuhiro Isogai, Kirti Sharma, Shoei Maeda, Hinako Akashi, Yui Sugai, Masataka Nakano, Noriyuki Kodera, Manish Biyani, Miki Nakajima, High-speed atomic force microscopy and 3D modeling reveal the structural dynamics of ADAR1 complexes, Nature Communications 16, 4757 (2025). DOI：10.1038/s41467-025-59987-6 URL: Funding and AcknowledgementsFinancial support from the Grants-in-Aid for Scientific Research (C), KAKENHI, Japan Society for the Promotion of Science (JSPS) (23K06067 to MadhuB), and the World Premier International Research Center Initiative (WPI), MEXT, Japan, are gratefully acknowledged. The authors thank Prof. Toshio Ando, Dr. Kenichi Umeda, Ms. Wei Weilin, Ms. Aimi Makino, and Ms. Kayo Nagatani for their technical support of HS-AFM experiments. Contact Kimie Nishimura (Ms)Project Planning and Outreach, NanoLSI Administration OfficeNano Life Science Institute, Kanazawa UniversityEmail: nanolsi-office@ Kanazawa 920-1192, Japan About Nano Life Science Institute (WPI-NanoLSI), Kanazawa UniversityUnderstanding nanoscale mechanisms of life phenomena by exploring "uncharted nano-realms". Cells are the basic units of almost all life forms. We are developing nanoprobe technologies that allow direct imaging, analysis, and manipulation of the behavior and dynamics of important macromolecules in living organisms, such as proteins and nucleic acids, at the surface and interior of cells. We aim at acquiring a fundamental understanding of the various life phenomena at the About the World Premier International Research Center Initiative (WPI)The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS). See the latest research news from the centers at the WPI News Portal: WPI program site: About Kanazawa UniversityAs the leading comprehensive university on the Sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since it was founded in 1949. The University has three colleges and 17 schools offering courses in subjects that include medicine, computer engineering, and humanities. The University is located on the coast of the Sea of Japan in Kanazawa, a city rich in history and culture. The city of Kanazawa has a highly respected intellectual profile since the time of the fiefdom (1598-1867). Kanazawa University is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students, including 600 from View original content: SOURCE Kanazawa University
Yahoo
10-06-2025
- Business
- Yahoo
Keros Therapeutics' Quiet Near-Term Outlook Overshadows Pipeline Potential: Analyst
Bank of America Securities analyst Jason Zemansky downgraded Keros Therapeutics, Inc. (NASDAQ:KROS) from Buy to Neutral, lowering the price forecast from $32 to $18. Zemansky noted that Keros has wrapped up its strategic review, with the board deciding to advance KER-065 for Duchenne muscular dystrophy (DMD) and return $375 million in excess capital to shareholders. The analyst highlights that the stock has been downgraded not due to concerns about the platform or pipeline, which remains compelling, but because of limited near-term favorable valuation and a solid cash buffer, Zemansky writes that the stock may stay range-bound given that meaningful updates on KER-065 are unlikely soon, with FDA discussions not expected until the third quarter. As a result, other investment opportunities may offer better near-term potential. The analyst slashed the price forecast to reflect adjustments to the cash balance and a higher weighted average cost of capital (WACC) of 16%, now aligned with peers at a similar stage. On June 9, 2025, ADAR1 Capital Management, the largest shareholder of Keros Therapeutics, stated that the recent board election results signal 'widespread dissatisfaction' among investors. ADAR1 highlighted that two directors received support from only about a third of outstanding shares, reflecting a loss of confidence in the board's management and capital allocation. While acknowledging Keros's recent decision to halt a drug program and cut staff, ADAR1 called the actions 'wholly insufficient.' The firm heavily criticized the board's plan to return only a portion of its cash to shareholders, arguing the amount retained is excessive for Keros's limited clinical pipeline. To address this, ADAR1 issued specific demands for the board to take immediate action. The firm called for Keros to increase its capital return by an additional $100 million for a total of $475 million, to be paid through a special dividend by the end of Q3 2025. Furthermore, ADAR1 urged the company to create a contingent value right (CVR) to allow shareholders to directly benefit from the Takeda partnership. ADAR1 warned that if the board does not adopt a more aggressive, investor-focused strategy, it will not hesitate to nominate new directors for the 2026 annual meeting to ensure the will of shareholders is respected. Zemansky acknowledged that the board had limited strategic options aside from fully dissolving the company. However, he writes that bearish investors may have expected a more aggressive outcome than just the potential $375 million capital return, especially since the exact structure and terms of the buyback remain undecided. Zemansky pointed out that beyond the longer development timelines, overall sentiment toward Keros likely remains cautious, which could continue to pressure the stock. While the company's three board nominees were elected despite activist opposition, a notable portion of votes were withheld for the two targeted candidates, indicating lingering investor discontent. He stresses the point that frustration may persist, particularly given the recent setback with TROPOS and skepticism that last month's cost-cutting measures were sufficient. Although some bulls might argue that the stock has been unfairly punished, especially given the added hurdles of developing drugs that target the TGF-β pathway, Zemansky writes most investors will likely wait for more meaningful progress and risk reduction before 'returning to the story.' Price Action: KROS shares are trading lower by 2.34% to $13.76 at last check Tuesday. Read Next:Image via Shutterstock Date Firm Action From To Dec 2020 SVB Leerink Maintains Outperform Dec 2020 HC Wainwright & Co. Maintains Buy May 2020 Piper Sandler Maintains Overweight View More Analyst Ratings for KROS View the Latest Analyst Ratings UNLOCKED: 5 NEW TRADES EVERY WEEK. Click now to get top trade ideas daily, plus unlimited access to cutting-edge tools and strategies to gain an edge in the markets. Get the latest stock analysis from Benzinga? This article Keros Therapeutics' Quiet Near-Term Outlook Overshadows Pipeline Potential: Analyst originally appeared on © 2025 Benzinga does not provide investment advice. All rights reserved.
Yahoo
09-06-2025
- Business
- Yahoo
ADAR1 Issues Statement on Keros Therapeutics' Troubling 2025 Director Election Results and Insufficient Capital Return Proposal
Significant Withhold Votes from Directors Mary Ann Gray and Alpna Seth Underscores Need for Change and a More Disciplined Capital Allocation Strategy AUSTIN, Texas, June 9, 2025 /PRNewswire/ -- ADAR1 Capital Management, LLC (together with its affiliates, "ADAR1" or "We"), the largest stockholder of Keros Therapeutics (Nasdaq: KROS) ("Keros" or the "Company"), today issued the following statement regarding the results of the Company's 2025 Annual Meeting of Stockholders (the "Annual Meeting"): "We believe the outcome of the Annual Meeting underscores what we have consistently conveyed to Keros' Board of Directors: there is broad and growing concern among stockholders regarding the Board's capital allocation decisions and fidelity to stockholder interests. ADAR1 previously disclosed its intention to withhold votes from Dr. Mary Ann Gray and Dr. Alpna Seth at the Annual Meeting. These two directors received among the highest level of shareholder opposition of any directors standing for election in 2025. In our view, this result reflects a substantial loss of stockholder confidence in the Board and clear dissatisfaction with the status quo. With only approximately 34% of outstanding shares voting to elect Dr. Gray and only 37% voting to elect Dr. Seth, the Board must recognize the widespread dissatisfaction with its stewardship of the Company. We appreciate the Company's recent decision to discontinue development of cibotercept in pulmonary arterial hypertension and, finally, implement a reduction in headcount. While these delayed actions are directionally positive, they are wholly insufficient and, in our view, are overshadowed by the Board's baffling decision to return only a modest portion of the Company's excess capital to stockholders. We can think of no credible justification for the Company to retain approximately half of its cash balance given its limited clinical pipeline and commercial prospects. In fact, at an investor conference today, CEO Jasbir Seehra acknowledged that the capital being held exceeds what is needed to fund the Company's current DMD program and may instead be used to pursue other high risk, hyper-competitive indications. Even more troubling is the lack of detail around the proposed capital return ― including the Board's failure to specify the terms, timing and method ― despite its claims to have completed a "thorough" and "comprehensive" review of strategic alternatives. In our view, this reflects a haphazard and incoherent approach to decision-making. In order for the Board to follow through on its stated commitment to maximizing value, it must take immediate and concrete action to reduce costs more aggressively, commit to returning $475 million (i.e., an additional $100 million over the currently proposed amount) to stockholders through a special dividend by the end of Q3 2025, and ensure that stockholders can directly capture the potential cash flow from the Takeda partnership through a contingent value right or similar mechanism, which should be implemented no later than year-end. ADAR1 continues to believe Keros possesses significant upside potential. But realizing that potential will require fresh perspectives in the boardroom and a disciplined, investor-focused approach to capital stewardship. Shareholders have spoken and the current directors do not have the support of a majority of shareholders. If the Board nevertheless insists on clinging to a failed strategy, ADAR1 will not hesitate to hold it accountable, including by nominating new directors for election at the 2026 Annual Meeting. We are committed to ensuring that the will of investors is not ignored, and we will continue engaging with the Company and our fellow investors to see that the desires of stockholders are heard and respected." About ADAR1 Capital ManagementADAR1 Capital Management is an SEC-registered investment manager based in Austin, Texas, focused on public and private equity investments in the life sciences and biotechnology sectors. The firm was founded in October 2018 by Dr. Daniel Schneeberger, who brings over 20 years of experience spanning scientific research, healthcare consulting, institutional investing, and executive leadership in the healthcare industry. He is supported by a team of experienced professionals with deep medical and scientific expertise and a strong track record of biopharmaceutical investing. Contact:info@ View original content: SOURCE ADAR1 Capital Management, LLC
Business Wire
03-06-2025
- Business
- Business Wire
Redwire Awarded Contract from Aspera Biomedicines to Investigate Cutting-Edge Cancer Treatment in Space
JACKSONVILLE, Fla.--(BUSINESS WIRE)--Redwire Corporation (NYSE: RDW), a leader in space infrastructure for the next generation space economy, announced today that it has been awarded a contract from Aspera Biomedicines, Inc. (Aspera), a pharmaceutical company specializing in the development of cancer stem cell targeted therapies, to conduct space-based research and analysis on a new cancer treatment using Redwire's Pharmaceutical In-space Laboratory (PIL-BOX) technology. Aspera will use this mission to advance development of rebecsinib, a small molecule ADAR1 inhibitor recently approved by the U.S. Food and Drug Administration to begin first-in-human trials. On Earth, scientists have noted an upregulation – or increased rate of expression – of the ADAR1 protein in cancer stem cells as being linked to the accelerated progression of some types of cancer. Researchers at Aspera have analyzed data from two previous spaceflight experiments that showed that rebecsinib can inhibit expression of ADAR1, halting the progression of cancer stem cell propagation in triple-negative breast cancer organoid models. Results from Aspera's prior experiments indicate that rebecsinib could behave as a cancer 'kill switch.' On this mission, Aspera researchers will analyze the crystal structure of ADAR1p150 with and without rebecsinib or intermediates. The results of this analysis could enhance opportunities to develop new drug formulations and a broader array of ADAR1 inhibitors. 'Redwire is excited to facilitate critical space research for Aspera Biomedicines' cutting-edge cancer treatment that could have major implications in the global fight against cancer,' said Redwire's President of In-Space Industries John Vellinger. 'Redwire's PIL-BOX technology continues to be a critical resource for enabling game-changing discoveries to advance human health.' 'At Aspera, it is a privilege to partner with our industrious and innovative colleagues at NASA, CASIS, and Redwire, through a NASA In Space Phase 2 biomanufacturing grant, to utilize microgravity to enhance and accelerate protein crystallization of the target of our FDA IND-approved small molecule inhibitor of the cancer cloning and immune evasion gene, ADAR1p150,' said Aspera's co-founder, Catriona Jamieson. 'We anticipate that this unique partnership combined with the science accelerating environment of the NASA International Space Station will extend the spectrum of small molecule 'cancer kill switches' aimed at preventing cancer stem cell cloning and immune evasion properties that drive relapse, the leading cause of cancer-related mortality.' With 28 units flown and processed to date, PIL-BOX is the premier platform for pharmaceutical researchers, leveraging the microgravity environment to grow small-batch crystals of protein-based pharmaceuticals and other key pharmaceutically relevant molecules. Previous PIL-BOX investigations conducted with partners including Bristol Myers Squibb, ExesaLibero Pharma, Eli Lilly and Company, and Butler University have focused on unlocking insights to improve treatments for cardiovascular disease, obesity, and diabetes. The Aspera cancer treatment investigation is slated to launch later this year. About Redwire Redwire Corporation (NYSE:RDW) is a global space infrastructure and innovation company enabling civil, commercial, and national security programs. Redwire's proven and reliable capabilities include avionics, sensors, power solutions, critical structures, mechanisms, radio frequency systems, platforms, missions, and microgravity payloads. Redwire combines decades of flight heritage and proven experience with an agile and innovative culture. Redwire's approximately 750 employees working from 17 facilities located throughout the United States and Europe are committed to building a bold future in space for humanity, pushing the envelope of discovery and science while creating a better world on Earth. For more information, please visit About Aspera Biomedicines Aspera Biomedicines was founded in San Diego in 2020 to develop cancer stem cell targeting small molecule inhibitors together with platform technologies that detect normal stem cell fitness and precancer and cancer stem cell development. With the California Institute for Regenerative Medicine (CIRM), NASA, and angel investor support, Aspera is the first company to develop an FDA IND approved small molecule inhibitor of ADAR1 splicing for myelofibrosis and acute myeloid leukemia that may also have implications for preventing recurrence and immune evasion in 20 cancers. By using microgravity to accelerate tumor growth with NASA and CASIS supported platforms as well as a dedicated collaborative partnership with Axiom Space, Aspera aims to investigate an expanded group of tumor indications for rebecsinib in patient derived tumor organoids to prevent the leading causes of cancer mortality—therapeutic resistance-related recurrence and metastases.
Yahoo
03-06-2025
- Business
- Yahoo
Redwire Awarded Contract from Aspera Biomedicines to Investigate Cutting-Edge Cancer Treatment in Space
JACKSONVILLE, Fla., June 03, 2025--(BUSINESS WIRE)--Redwire Corporation (NYSE: RDW), a leader in space infrastructure for the next generation space economy, announced today that it has been awarded a contract from Aspera Biomedicines, Inc. (Aspera), a pharmaceutical company specializing in the development of cancer stem cell targeted therapies, to conduct space-based research and analysis on a new cancer treatment using Redwire's Pharmaceutical In-space Laboratory (PIL-BOX) technology. Aspera will use this mission to advance development of rebecsinib, a small molecule ADAR1 inhibitor recently approved by the U.S. Food and Drug Administration to begin first-in-human trials. On Earth, scientists have noted an upregulation – or increased rate of expression – of the ADAR1 protein in cancer stem cells as being linked to the accelerated progression of some types of cancer. Researchers at Aspera have analyzed data from two previous spaceflight experiments that showed that rebecsinib can inhibit expression of ADAR1, halting the progression of cancer stem cell propagation in triple-negative breast cancer organoid models. Results from Aspera's prior experiments indicate that rebecsinib could behave as a cancer "kill switch." On this mission, Aspera researchers will analyze the crystal structure of ADAR1p150 with and without rebecsinib or intermediates. The results of this analysis could enhance opportunities to develop new drug formulations and a broader array of ADAR1 inhibitors. "Redwire is excited to facilitate critical space research for Aspera Biomedicines' cutting-edge cancer treatment that could have major implications in the global fight against cancer," said Redwire's President of In-Space Industries John Vellinger. "Redwire's PIL-BOX technology continues to be a critical resource for enabling game-changing discoveries to advance human health." "At Aspera, it is a privilege to partner with our industrious and innovative colleagues at NASA, CASIS, and Redwire, through a NASA In Space Phase 2 biomanufacturing grant, to utilize microgravity to enhance and accelerate protein crystallization of the target of our FDA IND-approved small molecule inhibitor of the cancer cloning and immune evasion gene, ADAR1p150," said Aspera's co-founder, Catriona Jamieson. "We anticipate that this unique partnership combined with the science accelerating environment of the NASA International Space Station will extend the spectrum of small molecule 'cancer kill switches' aimed at preventing cancer stem cell cloning and immune evasion properties that drive relapse, the leading cause of cancer-related mortality." With 28 units flown and processed to date, PIL-BOX is the premier platform for pharmaceutical researchers, leveraging the microgravity environment to grow small-batch crystals of protein-based pharmaceuticals and other key pharmaceutically relevant molecules. Previous PIL-BOX investigations conducted with partners including Bristol Myers Squibb, ExesaLibero Pharma, Eli Lilly and Company, and Butler University have focused on unlocking insights to improve treatments for cardiovascular disease, obesity, and diabetes. The Aspera cancer treatment investigation is slated to launch later this year. About Redwire Redwire Corporation (NYSE:RDW) is a global space infrastructure and innovation company enabling civil, commercial, and national security programs. Redwire's proven and reliable capabilities include avionics, sensors, power solutions, critical structures, mechanisms, radio frequency systems, platforms, missions, and microgravity payloads. Redwire combines decades of flight heritage and proven experience with an agile and innovative culture. Redwire's approximately 750 employees working from 17 facilities located throughout the United States and Europe are committed to building a bold future in space for humanity, pushing the envelope of discovery and science while creating a better world on Earth. For more information, please visit About Aspera Biomedicines Aspera Biomedicines was founded in San Diego in 2020 to develop cancer stem cell targeting small molecule inhibitors together with platform technologies that detect normal stem cell fitness and precancer and cancer stem cell development. With the California Institute for Regenerative Medicine (CIRM), NASA, and angel investor support, Aspera is the first company to develop an FDA IND approved small molecule inhibitor of ADAR1 splicing for myelofibrosis and acute myeloid leukemia that may also have implications for preventing recurrence and immune evasion in 20 cancers. By using microgravity to accelerate tumor growth with NASA and CASIS supported platforms as well as a dedicated collaborative partnership with Axiom Space, Aspera aims to investigate an expanded group of tumor indications for rebecsinib in patient derived tumor organoids to prevent the leading causes of cancer mortality—therapeutic resistance-related recurrence and metastases. View source version on Contacts Media Contacts: Emily Devine 305-632-9137 Investors: investorrelations@ 904-425-1431 Aspera:kmack@ Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
