Medical Billing and Finance Analyst
About the job
- A bachelor's-level degree or equivalent in Finance, Economics, Business Administration, Accounting, Health Care Financing, or a related field.
- Three to five years of federal claiming, medical billing, or other related financial experience.
- Demonstrated ability to create complex spreadsheets and reports using Microsoft Excel, Microsoft Access, and other available systems as necessary.
- Strong analytical and auditing skills.
- Proven competence in independent problem solving and quality control measures.
- Demonstrated ability to handle details, multitask, and prioritize work.
- Strong organizational skills and the ability to prioritize and coordinate multiple tasks and meet deadlines in a dynamic environment.
- Excellent interpersonal skills.
- Develop and maintain data-driven financial, claim-related, and program performance reports for internal management and external client audiences.
- Perform compliance reviews of program data, including claims, payments, and payment or cost settlement report data, for quality assurance and program integrity purposes.
- Analyze large, complex datasets to quantify and resolve problems, inform management decisions, monitor program changes and their impact, and communicate important information to internal management and external clients.
- Apply knowledge of program systems to identify and troubleshoot issues, participate in testing software changes, and assist clients and external users in effectively using program systems and applications.
- Assist in designing and maintaining internal controls to ensure the quality and accuracy of the business unit's work products.
- Compile and review claims, payments, and other financial data for approval or distribution.
- Identify and resolve discrepancies, questions, or outstanding issues related to claims, payments, or other financial data for approval or distribution, coordinating with internal staff, health plans, clients, or systems staff.
- Prepare financial and claims data for final submission and ensure its accuracy and compliance with regulatory, financial, and contractual requirements.
- Apply knowledge of state and federal program requirements, program guidelines, and reimbursement methodologies in all aspects of the work.
- Design and produce ad-hoc reports for internal management and client data requests, decision-making, and public records requests.
- Complete and synthesize analyses of claims, payments, and other financial data for reporting to internal and external stakeholders.
- Communicate program information and explain requirements and methodologies to clients and external users of UMass Chan systems and applications.
- Complete tasks required for operational, financial, and contractual deadlines, including setting up and maintaining claiming variables and notifying clients and stakeholders of deadlines, claim status, and required actions.
- Preserve confidential, protected health, and personally identifiable information and files.
- Perform related duties as needed and assigned.
About the company
UMass Chan Medical School operates as a public academic health sciences center that trains healthcare professionals, conducts biomedical research, and provides consulting services to government and nonprofit agencies. Through its MassBiologics division, it functions as the only nonprofit, FDA-licensed manufacturer in the U.S. to develop and produce vaccines and monoclonal antibodies. This integration of a graduate school with a large-scale manufacturing facility allows the institution to move medical discoveries directly from the lab to public production. The organization's goal is to advance medicine and improve community health by combining education, clinical trials, and specialized care management.
Company Size
5,001-10,000
Company Stage
Grant
Total Funding
$182.6M
Headquarters
Worcester, Massachusetts
Founded
1962
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Simplify's Take
What believers are saying
- August 2026 MLSC grants fund pregnancy AI tools and a colorectal cancer biobank.
- TNX-4800 Lyme antibody reached Phase 1; Phase 2 starts in 2027 pending FDA.
- SCD gene-editing alliance with Caring Cross and Trenchant targets IND work in 2027.
What critics are saying
- 2025 federal funding cuts furloughed 200 workers and shrank the PhD class.
- February 2026 USDA citations and PETA complaints threaten NIH animal-assurance status.
- If grant volatility persists into 2027, UMass Chan's research engine breaks and talent leaves.
What makes University of Massachusetts Medical School unique
- UMass Chan combines MassBiologics, RNA therapeutics, and clinical cardiology under one roof.
- David McManus started June 2026, bringing digital medicine and AI leadership.
- Its 2026 mRNA pancreatic cancer work shows rare depth in translational immunotherapy.
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Company News
Pancreatic Cancer disappears in mice after new mRNA immunotherapy. By Jim Fessenden, UMass Chan Medical School September 24, 2026 No Comments 5 Mins Read Pancreatic tumors vanished in roughly half of mice given an experimental mRNA therapy and did not return for up to a year after treatment stopped. Researchers at UMass Chan Medical School developed an experimental treatment for pancreatic cancer that uses a cocktail of messenger RNAs (mRNA) to activate immune defenses, break through the protective tissue surrounding tumors, and help immune cells recognize cancer cells as threats. Inspired by work at the school's RNA Therapeutics Institute and advances in COVID vaccines, the approach combines several immune signals and tumor-associated antigens in a single formulation. The study, published in Nature Communications, combined mRNAs encoding five immune cytokines with three tumor-associated antigens in one injectable treatment. Approximately 50 percent of mice with pancreatic ductal adenocarcinoma experienced complete tumor regression and remained disease-free for a year, including after therapy was discontinued. "It's unheard of to get a response like this in these models of pancreatic cancer," said Dr. Parikh, a recent PhD graduate from the Ruscetti Lab. "There have been a lot of drugs tried in the lab that have had good initial responses in mice, but ultimately the cancer always comes back. This is the only study I've seen that has achieved durable tumor protection." A rare response in Pancreatic Cancer. Results in mice do not guarantee that a treatment will succeed in people, particularly against a cancer as biologically complex as pancreatic ductal adenocarcinoma. Ruscetti nevertheless believes the strategy is promising enough to pursue toward clinical testing. Dr. Ruscetti, associate professor of molecular, cell & cancer biology, added, "Going from mice into patients takes a huge effort and is never a sure thing. However, if there was one approach I had to bet on being successful, this is the one. And that's what we're doing." Pancreatic ductal adenocarcinoma is the most common and aggressive form of pancreatic cancer. It begins in the narrow ducts that carry digestive fluids out of the pancreas. Early symptoms are often subtle or absent, allowing tumors to grow or spread to other organs before they are detected. The five-year survival rate is 3 percent for stage IV disease and 13 percent when all stages are combined. Why immunotherapy often falls short. Immunotherapies have transformed care for certain cancers by directing the body's defenses against malignant cells. Pancreatic tumors, however, have largely resisted these treatments because they create an unusually hostile environment around themselves. One major obstacle is a thick layer of fibrotic tissue surrounding the tumor. This structure functions like a castle wall, limiting the ability of immune cells to reach and attack the cancer. Even when immune cells enter, they must remain active long enough to mount a defense and distinguish tumor cells from healthy tissue. "All these steps are lacking in pancreatic cancer," said Ruscetti. "That's where the mRNA comes into play." Delivering immune signals where they matter. Cytokines are small signaling proteins, including interleukins, interferons, and tumor necrosis factors, that recruit and activate immune cells. Researchers experimented with cytokines as cancer treatments during the 1980s and 1990s, but the drugs often stimulated immune activity throughout the body. The resulting system-wide reactions could cause dangerous side effects while still failing to eliminate most tumors. Scientists now have a clearer understanding of which cytokines mobilize immune responses against particular threats, including pancreatic cancer. The remaining challenge is delivering the right signals where they are needed. "What we need is a way to get these immune signals to the tumor so they can do their job," said Ruscetti. mRNA offers a temporary set of genetic instructions that cells can translate into proteins. Rather than supplying cytokine and antigen proteins directly, the experimental treatment instructs cells to produce them. The cytokine mRNAs are intended to activate an immune attack, while the tumor antigen mRNAs help immune cells "see" pancreatic cancer as foreign material that should be removed. After the mice received the combination of five cytokine mRNAs and three tumor antigen mRNAs, the researchers observed less fibrotic material around the tumors and increased tumor cell necrosis. These findings indicate that the treatment both weakened the tumor's physical defenses and promoted cancer cell death. Immune memory may keep cancer away. Approximately half of the treated mice achieved complete remission that continued for up to one year after treatment stopped. The prolonged protection suggests that their immune systems may have developed a long-term "memory" of the cancer cells, potentially allowing them to recognize and attack the disease if it returned. Researchers could potentially change the mRNA sequences to produce cytokines and antigens suited to other tumors, creating different versions of the treatment for cancers that resist existing immunotherapies. "This is a first-of-its-kind approach combining cytokine mRNAs with tumor-associated antigen mRNA that could pave the path for effective immunotherapy for pancreatic ductal adenocarcinomas," said Parikh. "Beyond this cancer, this mRNA immunotherapy strategy has the capacity to be modular and can potentially be used as a platform to treat other types of immune-resistant cancers simply by swapping out different mRNA sequences." Reference: "Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against pancreatic cancer" by Chaitanya N. Parikh, Kelly D. DeMarco, Nikita Bhalerao, Hadiya K. Giwa, Griffin I. Kane, Ronnie W. Dinnell, Boyang Ma, Haruka Mori, Meghan L. Brassil, Katherine C. Murphy, Zhen Zhao, Calvin Johnson, Shriram Ramani, Lin Zhou, Loretah Chibaya, Youwei Qiao, Kai Hu, Lihua Julie Zhu, Brian C. Lewis, Wen Xue, Jason R. Pitarresi, Prabhani U. Atukorale and Marcus Ruscetti, 19 June 2026, Nature Communications. DOI: 10.1038/s41467-026-74574-z Initial funding for the study was provided by the Worcester-based Pancreatic Cancer Alliance, a patient advocacy group that supports pancreatic cancer research at UMass Chan. Researchers are now developing a potential IND-ready product of the cocktail in preparation for future clinical trials.
Welcome new pathology faculty! The Department of Pathology is pleased to welcome our outstanding new faculty members who will further strengthen our already outstanding team. Together our faculty community - both longstanding and new - will continue to advance our mission to deliver high-quality diagnostics, drive impactful research, and train the next generation of pathologists. We are delighted to introduce our newest colleagues and look forward to the many contributions they will make to our department and broader academic community. Adriano Piris, MD, is an expert dermatopathologist with extensive experience in the academic and private sectors. He joins the dermatopathology group where he will sign out routine cases, intramural and extramural consults, and will actively participate in the academic and teaching activities within the department. He is a graduate from the Medical School of the Universidad Nacional de Asuncion in Paraguay. He completed postgraduate training at Berkshire Medical Center and Massachusetts General Hospital (MGH Anatomic Pathology), and BIDMC (Dermatopathology). He is a former Assistant Professor in Dermatology at Harvard Medical School and former Director of the Mihm Cutaneous Pathology Consultative Service at Brigham Dermatology. He is currently a senior dermatopathology consultant for Sonic Health Care USA. He has worked with the Melanoma Group of the National Cancer Institute in Milan, Italy. Most recently, in collaboration with the Mohs micrographic surgery unit at Brigham and Women's Dermatology, he developed the first and only scoring system for desmoplasia in cutaneous squamous cell carcinoma, a work recently published in the Journal of Investigative Dermatology. Elena Brachtel, MD, PhD, is an internationally recognized breast pathologist and cytopathologist with extensive experience in academic medicine, clinical practice, research, and education. Dr. Brachtel will be stepping into the role of Co-Director, Breast Pathology. She joins us from the University of Miami Miller School of Medicine and has previously held faculty appointments at Massachusetts General Hospital and Harvard Medical School. Her clinical and research interests focus on breast pathology, breast cancer diagnostics, cytopathology, biomarker testing, and emerging technologies in cancer diagnosis. Throughout her career, Dr. Brachtel has made significant contributions to advancing breast cancer pathology, authored numerous peer-reviewed publications, and served in leadership roles in fellowship training and subspecialty pathology services. She is widely recognized for her commitment to trainee education, multidisciplinary collaboration, and innovation in diagnostic pathology. We look forward to her contributions to our clinical, educational, and research missions. Xia Qian, MD, joins our Dermatopathology team. She completed her AP/CP Residency and Dermatopathology Fellowship at BIDMC. She earned both her MD and PhD from Nanjing Medical University in Nanjing, China. She brings an extensive background in both clinical pathology and translational research, with prior work spanning cancer biology, liver disease, and gastrointestinal pathology. Her current research focuses on melanoma and inflammatory skin diseases, including the clinicopathologic features of mucosal melanoma and cutaneous syphilis. Maxwell Roth, MD, joins the Division of Laboratory and Transfusion Medicine as Assistant Director of the Blood Bank and Director of Transfusion Informatics. He received his MD from Albert Einstein College of Medicine and completed his residency in AP/CP at Massachusetts General Hospital. He subsequently completed a fellowship in Blood Banking/Transfusion Medicine at Mass General Brigham. His research focuses on informatics-based approaches to investigate transfusion medicine practices and outcomes in critically ill patients, as well as studying blood cell population dynamics. Before joining BIDMC, Xuefei Huang, MD, PhD, was an Assistant Professor of Pathology at UMass Chan Medical School with expertise in gastrointestinal, pancreatobiliary, liver, and liver transplant pathology. She began medical school at the age of 16 and earned an MD and PhD in China. Her doctoral research was among the first to demonstrate the therapeutic potential of Aurora kinase inhibition in acute myeloid leukemia, with the findings published in Blood. She was a postdoctoral fellow at MD Anderson Cancer Center and Boston Children's Hospital. She completed her AP/CP residency at UMass Chan Medical School, where she served as Chief Resident, followed by a fellowship in Gastrointestinal and Liver Pathology at Johns Hopkins Hospital. She has authored and co-authored numerous peer-reviewed publications in leading journals. Mai Elzieny, MD, joins the department as a faculty member in Anatomic Pathology, following a General Surgical Pathology fellowship at the David Geffen School of Medicine at UCLA and residency training in Anatomic and Clinical Pathology at Corewell Health William Beaumont University Hospital in Michigan. Dr. Elzieny earned her medical degree and master's degree in Clinical and Chemical Pathology from Ain Shams University Faculty of Medicine in Cairo, Egypt, where she also served as an Assistant Lecturer in Clinical Pathology. Her interests span surgical pathology, pathology education, quality improvement, and diagnostic innovation. She has contributed to a growing body of publications in areas including pathology informatics, artificial intelligence applications in pathology, laboratory medicine, and renal and liver pathology. Dr. Elzieny has also demonstrated a strong commitment to mentorship, diversity and inclusion initiatives, and trainee education throughout her career. Maxwell L. Harsha, PhD, DABCC, joins the Division of Clinical Laboratory Medicine as Assistant Director of Clinical Chemistry and Director of Diagnostic Endocrinology. Dr. Harsha comes to BIDMC from Johns Hopkins University School of Medicine, where he completed fellowship training in Clinical Chemistry and gained extensive experience in laboratory operations, clinical consultation, quality improvement, assay validation, and translational research. He earned his PhD in Environmental Analytical Chemistry from the University of New Orleans and his BS in Biochemistry from Loyola University Chicago. His research has spanned both analytical and clinical chemistry, with interests including diagnostic endocrinology, toxicology, therapeutic drug monitoring, and laboratory utilization. He has authored numerous peer-reviewed publications and presentations and has received several national trainee awards and recognitions. Sunati Sahoo, MD, joins the department as Director of Surgical Pathology, Co-Director of Breast Pathology, and Director, Specimen Biobank. Dr. Sahoo comes to BIDMC from UT Southwestern Medical Center where she was a Professor of Pathology. She led the breast pathology service and previously served as Director of Surgical Pathology at William P. Clements Jr. University Hospital. She earned her medical degree in India and completed postgraduate pathology training at the All India Institute of Medical Sciences in New Delhi, followed by residency training at New York-Presbyterian/Weill Cornell Medical Center. Dr. Sahoo's research has focused on neoadjuvant systemic therapy in breast cancer, prognostic and predictive biomarkers, and quality and outcomes research in breast disease management. Her arrival further strengthens BIDMC/HMFP Pathology's commitment to excellence in breast pathology, academic medicine, and multidisciplinary oncology care. Marina Vivero, MD, joins the department as a full-time attending pathologist in Anatomic Pathology, with subspecialty expertise in Thoracic Pathology and Cytopathology. Dr. Vivero comes to BIDMC from Brigham and Women's Hospital, where she served as an Associate Pathologist since 2015 and as an Assistant Professor of Pathology at Harvard Medical School since 2019. An internationally recognized expert in thoracic disease pathology and cytopathology, Dr. Vivero has made significant contributions to the diagnosis and classification of lung tumors, pulmonary neuroendocrine neoplasms, mesothelioma, and interstitial lung disease. Her research has helped advance the use of cytology specimens for molecular testing in lung cancer and has contributed to national and international diagnostic guidelines, including World Health Organization reporting systems and American Thoracic Society clinical guidance. In addition to her clinical and research accomplishments, Dr. Vivero has a longstanding commitment to education and mentorship. Kristine Wong, MD, joined Head and Neck and Cytopathology in early September. Widely recognized for her research, peer-reviewed publications, and lectures in thyroid pathology, endocrine pathology, head and neck pathology, and cytopathology, she joins us from BWH and is an Assistant Professor at Harvard Medical School. She attended Washington University School of Medicine and completed her AP/CP residency and Cytopathology fellowship at BWH. She is the co-author of the "Oncocytic Follicular Neoplasm" chapter of the Bethesda System for Reporting Thyroid Cytopathology, 3rd edition.
Women's Health spotlight: Massachusetts Preeclampsia Research & Equity Consortium (MAPREC). * September 3, 2026 Hypertensive disorders of pregnancy present ongoing challenges in how they are recognized, diagnosed, and managed. Through a rotating focus on specific disease areas, the Massachusetts Life Sciences Center's (MLSC) Women's Health Initiative is supporting research on Pregnancy-Induced Hypertension to address these challenges and improve care for pregnant and postpartum patients. These efforts build upon the MLSC's leadership in Women's Health with more than $29 million in investments across 21+ Massachusetts institutions. As part of a recent announcement of Women's Health Initiative awards, the MLSC supported the Massachusetts Preeclampsia Research & Equity Consortium (MAPREC), a collaboration bringing together leading researchers and clinicians from six institutions located throughout the Commonwealth. MAPREC is connecting four distinct, but complementary projects led by investigators at Massachusetts General Hospital (MGH), Beth Israel Deaconess Medical Center (BIDMC), Tufts University, Boston Medical Center (BMC), the University of Massachusetts (UMass) Amherst, and UMass Chan Medical School. MAPREC provides a structured platform for cross-site learning, model validation, and coordinated progress toward solutions for preeclampsia, a hypertensive disorder which affects an estimated 3% to 8% of women who give birth worldwide. By connecting research projects that take different approaches to understanding the condition, MAPREC aims to generate a multi-dimensional picture of how preeclampsia is experienced, recognized, and diagnosed, while creating opportunities for findings from each project to inform the development and testing of future interventions. Several MAPREC projects are leveraging artificial intelligence and machine learning to improve the prediction, identification, and management of hypertensive disorders of pregnancy across diverse clinical settings. One team, led by Mark Clapp, MD, of MGH, Taylor Freret, MD, of BIDMC, and Mohan Thanikachalam, MD, of Tufts University, is developing and validating an AI model using electronic health record data from more than 180,000 births to predict severe postpartum hypertension before patients leave the hospital. Complementing this work, BMC investigator, Sheree Boulet, DrPH, is using data from 15,000 pregnancies to develop machine learning models that could support the identification of early- and late-onset preeclampsia. Other projects are examining how a broader picture of each patient's experience can support more equitable care moving forward. At UMass Chan Medical School, Feifan Liu, PhD, and Crista E Johnson-Agbakwu, MD, are developing risk prediction tools and a clinical dashboard that incorporate electronic health record data and social determinants of health. At UMass Amherst, Lucinda Canty, PhD, is analyzing qualitative interviews with Black women and nurses alongside electronic health records from 25,000 pregnancies to examine diagnostic pathways and disparities in preeclampsia. According to a report from the McKinsey Health Institute, Black women in the United States are 60% more likely to develop preeclampsia, and face a five times greater risk of death from the condition. Together, these projects will inform the development and testing of multilevel interventions, including clinical decision-support tools, refined diagnostic criteria, and provider training strategies designed to enable earlier and more precise identification of preeclampsia. By examining the condition through both clinical data and the experiences of patients and providers, the consortium aims to develop solutions that reduce disparities and improve care for pregnant and postpartum patients across Massachusetts and beyond. By bringing together complementary expertise and research approaches from across the Commonwealth, MAPREC represents a coordinated effort to address complex challenges in preeclampsia care. As the Consortium's research progresses, its findings will help build a more comprehensive understanding of the condition and inform new approaches to identifying and caring for patients experiencing hypertensive disorders of pregnancy. Success Stories Featured in The Beat
Study: Cost savings, improved access to care seen with AI-based DR screening. September 01, 2026 Add topic to email alerts Key takeaways: * In an analysis, annual average cost savings per patient ranged from $2.70 to $155.90. * AI was comparable to or exceeded human graders in specificity and sensitivity. MONTEREY, Calif. - Alongside improved clinical efficiency and follow-up adherence, AI-based diabetic retinopathy screening yielded positive reductions in cost for patients, according to a poster presentation. The study, presented at the Women in Ophthalmology Summer Symposium, aimed to measure the impact of AI-based screening in DR, including its impact on clinical performance and patient economics, "with a focus on standardized cost-effectiveness across healthcare systems," Sophia Guccione, of UMass Chan Medical School, and colleagues wrote. The literature review used PubMed, Google Scholar and Scopus to compile studies that measured the diagnostic performance, patient perspectives or economic outcomes of AI-based screening between 2016 and 2025. The researchers analyzed standardized annual cost savings per patient in Australia, China, Singapore, Thailand and United Kingdom. According to the poster, AI-based screening for DR demonstrated sensitivity and specificity levels of more than 90% across multiple studies, "performing comparably to or exceeding human graders in diverse clinical settings." Through same-visit diagnosis and real-time analysis, primary care and community settings that implemented AI-based screening also showed improved follow-up adherence and screening completion. Modeled national savings exceeded $10 million annually, with absolute savings varying across healthcare systems, according to the poster. The study concluded that annual average cost savings per patient ranged from $2.70 to $155.90. Savings were attributed to reductions in transportation needs, missed workdays and out-of-pocket costs. "This suggests that health system-only analyses may underestimate the true value of AI-based screening," Guccione and colleagues wrote. While there are barriers to AI implementation, including inconsistent reimbursement framework and knowledge gaps among both patients and healthcare professionals regarding AI-based care, the researchers concluded that AI-based screening is a "scalable solution" for improving access, efficiency and outcomes for DR care. "High-income settings with higher labor costs generally showed larger per-patient savings, while lower-cost settings showed smaller but still positive gains," the researchers wrote. Perspective. At the recent Women in Ophthalmology Summer Symposium, Guccione and colleagues presented a literature review highlighting the advantages of AI-based diabetic retinopathy screening over conventional screening: excellent sensitivity (more than 90%) for detecting referable DR, improved follow-up adherence, and reduced patient burden from transportation, costs and work disruption. More than 40 million Americans have diabetes, and DR is the leading cause of vision loss among working-age adults. Given an ophthalmology workforce unable to keep pace with population needs, leveraging teleretinal screening makes sense; coupling it with AI makes even more sense. The benefits are well documented. So why has AI-based DR screening not taken off, despite FDA-approved systems being available for nearly a decade? The answer is multifactorial, but a major obstacle is the payment structure for teleretina, which remains prohibitive for a self-sustaining model. The reported cost savings of $2.70 to $155.90 per patient are comparable to what Healio has published. Yet these figures underestimate the broader economic value of earlier detection and treatment. This is the paradox of preventive medicine: Without a counterfactual, its value is difficult to see. Telemedicine can transform access to retina care. It's time for payer policies to recognize its worth - and for reimbursement to catch up with the evidence. References: Christina Y. Weng, MD, MBA, FASRS Healio | OSN Retina Board Member Baylor College of Medicine, Houston Disclosures: Weng reports no relevant financial disclosures. Published by: Sources/Disclosures. Guccione S, et al. Artificial intelligence in diabetic retinopathy screening: Clinical, patient, and economic perspectives. Presented at: Women in Ophthalmology Summer Symposium; Aug. 20-23, 2026; Monterey, California. Disclosures: Healio could not confirm relevant financial disclosures at the time of publication. Ask a clinical question and tap into Healio AI's knowledge base. * PubMed, enrolling/recruiting trials, guidelines * Clinical Guidance, Healio CME, FDA news * Healio's exclusive daily news coverage of clinical data
First mRNA flu shot approved by FDA bodes well for improving drugs of the future - though a few hurdles remain before... * Technology * 7 Aug 2026 4:24 am AEST * Share Vaccines have been reliably and affordably protecting people from diseases worldwide for centuries. Until the COVID-19 pandemic, however, vaccine development was still a long and idiosyncratic process. Traditionally, researchers had to tailor manufacturing processes and facilities for each vaccine candidate, and the scientific knowledge gained from one vaccine was often not directly transferable to another. * Li Li Assistant Professor of Biomedical Sciences, UMass Chan Medical School But the COVID-19 mRNA vaccines brought a new approach to vaccine development. And on Aug. 5, 2026, the U.S. Food and Drug Administration approved another mRNA vaccine - a seasonal flu vaccine for adults age 50 or older - that offers more protection against influenza compared to standard vaccines. These advances demonstrate the momentum of mRNA technology, and they have far-reaching implications for how researchers make drugs to treat many other diseases. Although there are many possibilities for what researchers can use mRNA to treat, some important limitations remain. My work as a biochemist and my lab at UMass Chan Medical School focus on developing better ways to use mRNA as a drug. Better understanding how mRNA-based drugs interact with the immune system and how they are degraded in human cells can help lead to safe, durable and effective treatments for a wide range of diseases. Some basics of mRNA drugs. Messenger RNA, or mRNA, is made of four building blocks denoted by the letters A, C, G and U. The sequence of letters in an mRNA molecule conveys genetic information that directs how a protein is made. Discover more Newspapers An mRNA drug comprises two essential components: mRNA molecules, which code for desired proteins, and the lipid molecules - such as phospholipids and cholesterol - that encapsulate them. These mRNA-lipid nanoparticles, or LNPs, are tiny spheres about 100 nanometers in diameter that protect mRNA from degradation and facilitate its delivery into target cells. Once inside cells, mRNA molecules instruct the cell's machinery to produce the target protein required for a desired therapeutic effect. For example, the mRNA in the Pfizer-BioNTech and Moderna COVID-19 vaccines directs cells to produce a harmless version of the virus' spike protein that trains the immune system to recognize and better prepare for potential infection. From a drug development perspective, mRNA drugs offer significant advantages over traditional drugs because they are easily programmable. Hundreds of pounds of mRNA can be made from readily available DNA templates, such that producing a different mRNA drug is as simple as changing the corresponding DNA templates. More importantly, different mRNA drugs produced by the same set of methods will have similar properties. They will be delivered to the same tissues, trigger similar levels of immune responses and degrade in similar ways. This predictability significantly reduces the development risks and financial costs of developing mRNA drugs. In addition to being easy to program, mRNA drugs have several other unique properties. For example, just like the mRNAs your body naturally produces, therapeutic mRNAs have a short half-life in cells: about one day. As a result, current mRNA technology is ideal for treatments that aren't meant to last long in the body. Discover more Government Beaches & Islands This is why vaccines are popular candidates for mRNA technology: They provide long-term protection against disease after brief exposure to the drug with few side effects. Self vs. nonself. Another critical feature of mRNA drugs is their intrinsic ability to stimulate the immune system. This may sound paradoxical - after all, your cells already contain large amounts of mRNAs. Why would other mRNAs activate your immune system? How does your immune system distinguish between self and nonself mRNAs? The first reason involves location. Therapeutic mRNAs enter cells using endosomes - sacs made of the cell's membrane that take in materials from the cell's environment. Your immune system can detect mRNA in endosomes because this is usually a sign of an RNA virus infection - cellular mRNAs normally don't enter endosomes. When your immune system labels therapeutic mRNAs as viral material, it triggers a strong inflammatory response that can lead to severe side effects. One solution to this problem is to modify mRNA's building blocks - specifically, changing the U, or uridine, to its chemical cousins, pseudouridine and N1-methylpseudouridine. This subtle chemical change prevents the unwanted immune response while allowing the therapeutic mRNA to direct the cell to make the protein it encodes. The 2023 Nobel Prize in physiology or medicine was awarded to the scientists who made this breakthrough discovery. Both the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines use this technique. The second source of unwanted immune response is impurities from mRNA production. To prepare mRNA from a DNA template, scientists use a protein called RNA polymerase that tends to make a small amount of side product called double-stranded RNA. Unlike mRNA, which is single-stranded, double-stranded RNA has two chains that form a double helix. RNA viruses also form double-stranded RNA when they replicate, and exposing cells to double-stranded RNA can lead to a strong immune response. Discover more Southeast Asians & Pacific Islanders Travel Guides & Travelogues Executive Branch Removing double-stranded RNA is challenging, especially at the industrial scale. Fortuitously, for mRNA vaccines, the residual amount of double-stranded RNA can stimulate the immune system to enhance antibody responses. However, for applications other than vaccines, a cleaner RNA product is necessary to reduce side effects. Moving beyond vaccines. Although mRNA has the potential to transform drug development for various medical purposes, careful consideration is required to identify targets that align with the technology's strengths. For example, because there is currently a limit to how long mRNA can last in the body, treatments that need a protein to be present for only a short period of time to achieve a lasting therapeutic effect are ideal. One promising example in development is using mRNA that encodes CRISPR-Cas9 gene-editing proteins to knock out genes that cause specific diseases. Researchers are exploring this strategy to develop a single-dose treatment for hereditary transthyretin amyloidosis, a rare genetic disease caused by the accumulation of misfolded proteins in the heart and nerves. This disease is an ideal target for mRNA-based CRISPR gene therapy because the target protein is produced by the liver. Because most drugs pass through the liver, this makes it easier to deliver CRISPR-Cas9 mRNA to its target. In the next few years, a new generation of more precise mRNA-based genome editing therapies will enter clinical trials. For treatments that need a specific protein to be present in the body for long periods of time or need to prompt little to no immune reaction, further advancements in mRNA technology are necessary to extend mRNA's half-life and eliminate immune-triggering contaminants. Notable new developments in these areas include using computational algorithms to optimize mRNA sequences in ways that enhance their stability and engineering RNA polymerases that introduce fewer side products that may cause an immune response. Further advancements have the potential to enable a new generation of safe, durable and effective mRNA therapeutics for applications beyond vaccines.