# data[].attributes.title
Development of a tissue-targeted non-thrombotic EPO derivative

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National Heart Lung and Blood Institute (NHLBI)

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“Development of a tissue-targeted non-thrombotic EPO derivative.”  Chronic obstructive pulmonary disease (COPD) affects 16 million people in the US and is the third leading cause of death in the world, with an estimated 500 million cases worldwide. In the US the primary cause is cigarette smoking, but in most of the world the cause is air pollution. In this disease, the airways (bronchioles) are constricted and the alveoli are distended and never fully contract. Current treatments use drug inhalers that open up the airways, but these treatments are only partially effective. In addition, about 2 million of the US COPD patients are also anemic, so that oxygen delivery is particularly poor.  Erythropoietin (EPO) is a hormone that mediates the body’s response to massive blood loss (hemorrhage). EPO is used to treat anemia in kidney failure, cancer, etc., based on its stimulation of red blood cell production. EPO also has a useful tissue-protective activity that can reduce effects of oxygen limitation that damage the heart, brain, and other tissues. However, EPO also enhances blood clotting and increases frequency of heart attacks, strokes and deep vein thrombosis when given to anemic patients.  To address COPD and other problems of oxygen delivery, General Biologics is developing an engineered protein, termed “EPO-H” (EPO for Hypoxia), that retains the red blood cell producing and tissue-protective activities of EPO, but lacks the blood clotting side effects. EPO-H will also have a long plasma half-life, to allow for infrequent dosing, patient convenience, and reduced burden on the health care system.  The net effect should be that, compared to current commercial versions of EPO, our protein (“EPO-H”) will maintain production of red blood cells, show increase neuroprotection, and have significantly reduced or eliminated blood-clotting site effects. Natural EPO is not currently given to COPD patients or patients with disorders such as cystic fibrosis or extreme Covid-19 requiring hospitalization and mechanical ventilation.  Our experimental aims are: (1) General Biologics will produce engineered protein for all of the experiments and will test the proteins for blood-based surrogate markers of hypoxia resistance and blood-clotting, to establish a dose at which the therapeutic effect is expected but side effects are not.; (2) University of Maryland will demonstrate that EPO-H can promote survival of mice in a low- oxygen environment; and also (3) demonstrate that EPO-H does not enhance clot size in a mouse model of deep vein thrombosis, even though natural EPO does increase the size of blood clots in mice with deep vein thrombosis.

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The impact of peer support in treatment engagement and adverse events for Medicaid beneficiaries with substance use disorder: a mixed-methods study

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Substance use disorder (SUD) due to drugs other than alcohol, which affects 9% of adults in the United States, is a significant public health concern contributing to substantial morbidity and mortality, resulting in over 100,000 overdoses in 2022 alone. While effective SUD treatment exists, fewer than 25% of people with SUD receive treatment. Peer support services (PSS) offer a potential avenue for enhancing SUD treatment and outcomes, with the goal of helping people with SUD initiate and remain engaged in the recovery process. These services, delivered by trained and credentialed peer specialists who have firsthand experience with SUD, encompass a wide range of support services, including recovery planning, community linkages, and social and emotional support services. PSS are unique to other types of care navigation in that they emphasize improving clients' psychosocial skills, including resilience, coping, and empowerment. PSS, which use a recovery coaching model, are also distinct from the peer support provided by uncredentialed sponsors in 12- step facilitation. Growing adoption of PSS has outpaced the evidence on the effectiveness of PSS, which is limited and mixed. Nowhere is this more evident than with Medicaid, the largest payer of SUD treatment services in the U.S. Medicaid is an innovator in coverage of PSS. In 2024, 41 state Medicaid programs covered PSS for adults with SUD, increasing from only 26 states in 2017. Medicaid's substantial expansion of PSS coverage and the urgent need for SUD treatment services within the Medicaid population creates an opportunity to rigorously evaluate the impact of receiving PSS on SUD treatment and SUD-related adverse outcomes. Furthermore, the COVID-era Medicaid policy changes that expanded telehealth coverage provide an avenue to compare the effectiveness of telehealth PSS relative to in-person delivered PSS. The overall goals of this study are to provide robust evidence on whether and how PSS impact SUD treatment engagement and outcomes and to inform the design of PSS coverage policy in Medicaid and other insurance programs. We will focus on the following specific aims to achieve these objectives: (1) Assess the impact of Medicaid-covered PSS on SUD treatment initiation, engagement, and retention among Medicaid beneficiaries with SUD, (2) Assess the impact of Medicaid PSS on adverse events including SUD-related emergency department visits, unplanned inpatient readmissions, and drug overdose among Medicaid beneficiaries with SUD; and (3) Characterize how Medicaid PSS coverage policies can influence PSS implementation for Medicaid beneficiaries with SUD. This proposed mixed-methods study will use a concurrent-embedded approach, such that quantitative results (Aims 1-2) will inform qualitative analyses (Aim 3) and vice versa at various points in the study. Study findings will build evidence on the impact of PSS on SUD treatment and overdose and inform the rapidly evolving landscape of PSS policy and implementation.

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How the endocytic network mediates specificity of cell signaling

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National Institute of General Medical Sciences (NIGMS)

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Abstract: How the Endocytic Network Mediates Specificity of Cell Signaling Receptor crosstalk – the cooperation between two or more receptors to modulate cell responses – is a key signaling mechanism. It enables cells to generate a large combinatorial repertoire of specific signaling with a limited variety of receptors. Receptor crosstalk plays an essential role in cell physiology. Consequently, dysfunctions in receptor crosstalk are associated with many human diseases, such as infectious diseases (including COVID-19), cancer, and cardiovascular diseases. To understand the physical mechanisms by which signals from different receptors are integrated in crosstalk, studies have exclusively focused on receptor interactions at the plasma membrane. In contrast, how the crosstalk signals are transduced with high fidelity from the plasma membrane to the nucleus is poorly understood and scarcely explored. The overall goal of this research is to establish the functional role of the endocytic network in transducing and regulating receptor crosstalk. During the past 6 years, our group has made pioneering discoveries in support of the central hypothesis that the endocytic network is where extracellular chemical and physical stimuli intertwine to regulate receptor crosstalk. Specifically, we reported a new model in which receptors can crosstalk by forming overlapping interfaces between discrete signaling clusters, challenging the prevailing view that receptors oligomerize to crosstalk. Importantly, such spatially organized interaction between receptors at endosomes and plasma membranes is modulated by extracellular physical cues, and directly regulates cell inflammatory responses. These prior discoveries and the plethora of new approaches we developed for studying endosome functions laid a critical and unique foundation for us to address the knowledge gap: how does the endocytic network mediate receptor crosstalk? We will address how the endocytic network orchestrates chemical cues from receptor crosstalk (Direction 1) and transduces extracellular physical cues to refine the specificity of crosstalk signaling (Direction 2). To address the first direction, we will define the physical mechanisms by which endocytic sorting, collective endosome-organelle interactions, and endosome-specific activation modulate crosstalk signaling originated from the plasma membrane. To address the second direction, we will integrate experiments with computational modeling to determine the feedback loop between the endocytic network and cell-matrix interactions that regulate receptor crosstalk. This project will establish a mechanistic and predictive understanding of how the endocytic network mediates the spatiotemporal specificity of receptor crosstalk and cell signaling in general; a topic that is poorly understood. It will also lower the technical barrier that has impeded research on this topic, by establishing novel quantitative toolsets for dissecting the dynamics and function of the endocytic network on multiple length scales. Ultimately, a better understanding of endosome functions in receptor crosstalk will facilitate the development of new therapeutic strategies for diseases.

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United States National Institutes of Health

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Increased Extraction Capacity for Molecular Section

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Vet-LIRN Network Capacity-Building Project and Equipment Grants (U18) PAR-23-202 Increased Extraction Capacity for Arizona Veterinary Diagnostic Laboratory Molecular Section Project Summary/Abstract- The Arizona Veterinary Diagnostic Laboratory (AZVDL) is seeking funding to purchase an Indical IndiMag2 to enhance its nucleic acid extraction capability and capacity, thereby strengthening its emergency surge testing for signiﬁcant animal food/feed emergency events. Veterinary diagnostic laboratories play a critical role in protecting both animal and public health, especially during large-scale foodborne disease outbreaks or contamination incidents. Funding through the Vet-LIRN Network Capacity-Building Project and Equipment Grants (U18) is essential to expand AZVDL’s ability to respond eﬀectively to such emergencies. This support will enable AZVDL to improve its diagnostic capabilities by acquiring advanced equipment. The COVID-19 pandemic has demonstrated that veterinary laboratories are uniquely positioned to provide high-throughput testing during public health crises, as they routinely handle large- scale diagnostic procedures for zoonotic and animal diseases. By enhancing its capacity, AZVDL will be better equipped to provide real-time detection of pathogens or contaminants in animal food and feed, helping to prevent outbreaks that threaten food safety, public health, and economic stability. This funding initiative also aligns with the goals of the Food Safety Modernization Act (FSMA), which emphasizes proactive measures to detect and prevent foodborne illnesses. Upgrading AZVDL’s infrastructure will not only improve its response to emerging threats but also contribute to the broader national network of veterinary laboratories dedicated to safeguarding both animal and human populations.

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Impacts of universal influenza mRNA vaccine on enhancing the efficacy of seasonal vaccination

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National Institute of Allergy and Infectious Diseases (NIAID)

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Current influenza (flu) vaccines based on immunity to variable hemagglutinin (HA) provide low efficacy because of continuing HA antigenic changes and poor cross-protection. The flu ion channel M2 protein ectodomain (M2e) represents highly conserved epitopes and the HA-stem (HA2-fusion) is also an immune target for conferring protection against different viruses. My mentor’s lab reported that heterologous (human, swine, avian) tandem repeat M2e protein (5xM2e) could be a cross-protective immunogen and chimeric M2e-stem protein vaccine conferred broad cross-group protection. Nonetheless, the prior 5xM2e and M2e- stem protein vaccines require high doses and need to add neutralizing immunity. COVID-19 mRNA vaccines have been approved to widely immunize six-month-old children to the elderly, validating mRNA vaccine modality. My preliminary mouse study demonstrated that 5xM2e mRNA and M2e-stem mRNA vaccines (encapsulated into lipid nanoparticles, LNP) effectively induced M2e and stem IgG antibody responses at a low dose. Most innovatively, I found that 5xM2e mRNA-LNP supplemented conventional inactivated split flu vaccination significantly enhanced the immunogenicity and efficacy with a single dose, probably via transient induction of innate cytokine and chemokines. These preliminary data warrant further investigation of this novel vaccination strategy of combining cross-protective flu mRNA and conventional flu vaccines, overcoming a weakness of each vaccine platform. As supported by my preliminary data, I hypothesize that neutralizing HA immunity (HA mRNA or split) plus universal target immunity (M2e-Stem mRNA or protein) will offer increased immunogenicity leading to enhanced protection against homologous and heterologous viruses. In aim 1, I will determine the immunogenicity and efficacy of protection against homologous and antigenically different flu viruses after HA-based (HA mRNA or split) plus cross-protective antigen (M2e-stem mRNA or protein) vaccination. For aim 2 approaches, I will investigate the immune mechanisms of mRNA-LNP supplemented split- and protein-based vaccines inducing enhanced protection. The potential mechanisms to study will determine the contribution of antigen-specific humoral and cellular immunity to cross-protection, and the innate immune responses (innate cell phenotypes, cytokines, chemokines), likely leading to enhanced adaptive immunogenicity of vaccines. The roles of Fc receptor (FcR), natural killer (NK) cells, and ADCC (antibody-dependent cell-mediated cytotoxicity) in conferring cross-protection will be determined by using mutant mice and in vitro assays. The expected outcome of this project will advance our knowledge of how mRNA-LNP supplemented conventional vaccine elicits enhanced efficacy. If successful, this project could open a new avenue for research in enhancing vaccine efficacy for other pathogens.

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United States National Institutes of Health

# data[].attributes.title
Single arm trial of menstrual cups among economically vulnerable women to reduce Bacterial vaginosis and STIs through reduced harmful sexual and menstrual practices

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National Institute of Allergy and Infectious Diseases (NIAID)

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In western Kenya, HIV prevalence is 16% among women in the general population, and 29% among the most economically constrained women. The HIV/STI epidemic overlaps with broader reproductive health concerns. Menstrual hygiene management (MHM) is a pervasive problem across low- and middle-income countries. In Phillips-Howards’ survey of over 3,400 women in rural Kenya, two-thirds of women in impoverished settings state they depend on their sexual partners to provide branded products. Economically vulnerable women at high risk for HIV and STI are uniquely challenged because many continue to have sex during menses, and engage in harmful MHM practices, such as vaginal insertion of sponges and cotton to maintain dryness. Led by co-investigator Phillips-Howard, a cluster-randomized study of 644 girls aged 14-16 years old in western Kenya compared reusable menstrual cups to usual menstrual practice and counseling; after 9 months, menstrual cup use resulted in 35% reduction (p=0.034) in Bacterial vaginosis (BV) prevalence and 56% reduction (p=0.001) in STI prevalence compared to other materials. Among 431 Kenyan secondary schoolgirls aged 14-21, we observed cloth use for menses was associated with a 1.72-fold increased odds of non-optimal vaginal microbiome (CST-IV vs. CST-I: aOR=1.90; 95% CI: 1.03–2.86). Over 18 months of observation prior to COVID-19, girls using menstrual cups to manage menses had 20% higher occurrence of Lactobacillus crispatus dominated CST-I (aRR=1.29; 95% CI: 1.08–1.53, controlling for age, and baseline STI and sexual activity). Menstrual cups designed for use during intercourse may help women prevent BV and STIs through hygienic menstrual practices and avoidance of harmful practices to maintain vaginal dryness during menses. Objective: This single-arm interventional trial seeks to evaluate the preliminary efficacy of menstrual cups on non-optimal vaginal microbiome (VMB), BV, and STIs of economically vulnerable women at high risk for STIs and HIV, assess safety profile, and understand implementation needs. In Aim 1, we will evaluate the impact of menstrual cups on VMB, BV, and STIs among 402 economically vulnerable women in semi-urban Kenya. In Aim 2, we will conduct integrated surveillance for enhanced detection of safety endpoints, risk of cup contamination, and mitigating or facilitating water, sanitation, hygiene (WASH) factors. In Aim 3, we will identify constructs for successful MHM program implementation using an implementation science framework. Future Directions: The biological protection suggested in a randomized setting, and our findings that unhygienic cloth use is associated with non-optimal VMB, while menstrual cup use increases optimal VMB composition, together provide rational justification for this trial, of relevance to economically challenged women globally. Assessing preliminary efficacy signal in conjunction with implementation characteristics and adverse events, will generate a comprehensive and necessary foundation for definitive assessment of effectiveness of menstrual cups as a multipurpose intervention for MHM, and to reduce BV and STIs.

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HIV and its impact on Long COVID prevalence and manifestations

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National Institute of Allergy and Infectious Diseases (NIAID)

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The purpose of this NIH F30 application is to support the PI, Skye Opsteen, and her mentored research and career development for the next three years. The proposed activities will strengthen her potential to become a successful physician scientist. The major goal of this project is to develop her experimental immunology skills to inform the biologic basis of post-COVID syndromes, particularly in people with HIV (PWH) given their increased baseline immune activation. The primary objectives of the research proposal are to investigate if the monocyte and T cell population shifts typical of chronic HIV infection are exacerbated during long COVID, and how the immune features of long COVID in PWH compare to people without HIV. Chronic inflammation has been implicated in long COVID development and is known to drive increased rates of comorbidities in PWH; therefore, studying long COVID in PWH offers a unique opportunity to characterize long COVID phenotypes driven by chronic inflammation. This project will investigate monocyte-mediated inflammation, specifically the role of CD16+ monocytes and inflammatory cytokines IL-1 and TNF in recovery versus long COVID development in PWH, and how these responses contribute to clinical symptoms such as fatigue (Aim 1). The project will also determine the contribution of adaptive immune responses during long COVID in PWH (Aim 2). Our long-term objective is to inform future long COVID studies of potential diagnostic markers and therapeutic targets for patients with long COVID phenotypes driven by persistent inflammation. The proposed training plan for the PI is sponsored by her primary PhD mentor, Dr. Nathan Erdmann, and co- mentor, Dr. Paul Goepfert. Included in the training plan are experiences that will help her develop in three major areas: 1) rigorous immunological research in HIV and SARS-CoV-2, which includes developing familiarity with the existing literature, critically evaluating published studies, and training in principles of scientific integrity and responsible conduct of research; 2) competence in bioinformatic techniques and biostatistical analysis; and 3) career and professional development, including grant writing, manuscript review, clear communication through presentation and manuscript preparation, and translation of research findings to clinical applications. After completion, this training plan will provide the PI with the foundation necessary for a successful career as a physician scientist. Her ultimate career goal is to one day lead a translational research laboratory that studies human immune responses to emerging and reemerging pathogens in the setting of chronic immune dysregulation to assist in the clinical prevention and treatment of various infectious diseases in at-risk populations.

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United States National Institutes of Health

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Multimodal Analysis of Gestational Health and Placental Injury in Opioid-Affected Pregnancies

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Opioids are medically used for safe pain relief and management. However, illicit opioid use has substantially increased across the US in the past decade, with further worsening during the COVID-19 pandemic, leading to a profound impact on human health. Specifically, opioid use disorder (OUD) during pregnancy poses an increased risk of pregnancy-associated maternal morbidity and mortality, fetal growth restriction (FGR) and related complications, neonatal opioid withdrawal syndrome, and long-term neurobehavioral effects. Some of these risks persist despite the use of safer opioids, such as buprenorphine and methadone, medications for OUD (MOUD) patients. Whereas current studies center mainly on transplacental opioid transport to the fetus and the adverse effects of opioids on infants, the direct impact of illicit and prescription opioids on placental development, differentiation, and function are largely unexplored. The placental floating villi mediate maternal- fetal gas exchange, nutrient uptake, waste release immune defense and the production of hormones and extracellular vesicles (EVs). These villi are covered by a layer of multinucleated, terminally differentiated syncytiotrophoblasts (STBs), which forms the feto-placental frontline that is directly exposed to opioids in the maternal blood. Subjacent to this layer are mononucleated, progenitor cytotrophoblasts (CTBs), which replenish the STB layer through the process of differentiation and fusion. Importantly, injuries to the STB and CTB layers are implicated in pregnancy-associated complications, including FGR and stillbirth. Here we seek to investigate opioid-dependent placental injury, focusing on the most critical and unique layer of placental trophoblasts. We will enroll participants with OUD, including illicit opioids and MOUD (buprenorphine, methadone), examine their pregnancy course and their children’s health through the first year postpartum. Using biospecimens from each participant, including maternal plasma and urine across the three trimesters, placental biopsies and fetal cord blood at delivery, we will employ multimodal cutting-edge technologies, including single-cell RNAseq, spatial transcriptomics, protein chip cytometry and placenta EV RNA profiling, and explore the molecular and cellular processes affected by opioids in the maternal-placental-fetal trio- ecosystem. To gain mechanistic insights into the functional changes in gene expression and EV cargo, we will use an array of model systems, including human trophoblast stem cells and cultured primary human trophoblasts, and mechanistically interrogate pathways underlying opioid injury. We will further correlate key molecular signatures with clinical assessment, including maternal gestational disorders, perinatal and infant neurodevelopmental outcomes. Together, our strategic plan, bolstered by our transdisciplinary team, enables us to address critically important knowledge gaps related to human placenta biology in opioid-affected pregnancies.

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Mechanisms of Pathogenesis in Staphylococcal Enterotoxin B-Induced Acute Respiratory Distress Syndrome

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National Institute of Allergy and Infectious Diseases (NIAID)

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UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA

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Acute Respiratory Distress Syndrome (ARDS) is a severe condition characterized by non-compliant lung, hypoxemia, protein-rich pulmonary edema, and cytokine storm. The COVID-19 pandemic highlighted ARDS as a significant public health burden that annually affects approximately 200,000 patients in the US with a 35-45% mortality rate. ARDS develops via a myriad of etiologies, though the most common underlying conditions in the US include pneumonia (44.9% of all cases) and nonpulmonary sepsis (46.8% of all cases). The gram-positive bacterial pathogen Staphylococcus aureus is one of the most commonly isolated pathogens in sepsis patients. S. aureus produces superantigens (SAgs), including Staphylococcal Enterotoxin B (SEB). SEB exposure can induce ARDS by activating up to 30% of the naïve T cell pool through the formation of non-specific cross-linkages between antigen-presenting cells (APCs) and T cells. The receptors involved in this interaction are classically believed to include Vβ TCRs, CD28, CD80/CD86, and MHC class II, though some studies suggest that MHC class II may be dispensable for inflammatory response. Interestingly, recent studies have demonstrated that the SARS-CoV-2 Spike protein contains a superantigen-like motif similar to SEB; additionally, the CDC has classified SEB as a Category B Biological Agent due to its ease of dissemination and inhalation toxicity. Therefore, murine models of SEB-induced ARDS can provide valuable insights into S. aureus and SARS-CoV-2 infection treatment, ARDS pathogenesis and prevention, and biological weapon response. My preliminary data demonstrates that the H2k C3H/HeJ mouse strain, but not the H2b C57BL/6J strain, are susceptible to SEB-induced ARDS, which suggests that H2 haplotype may play a role in superantigen response. Therefore, the central hypothesis of the proposed project is that C3H/HeJ mice are susceptible to SEB-induced ARDS due to alterations in MHC Class II, Vβ TCRs, CD28, or CD80/CD86, which allow SEB to more effectively form cross-linkages between APCs and T cells, thereby increasing SAg-mediated T cell activation and subsequent myeloid infiltration to the alveoli. To test this hypothesis, I propose the following specific aims: 1) Establish the cellular and molecular mechanisms of SEB-induced ARDS pathogenesis in C3H/HeJ and C57BL/6J mouse strains; 2) Determine whether strain-specific differences in MHC Class II, Vβ TCRs, CD28, or CD80/CD86 drives differential response to SEB in C3H/HeJ and C57BL/6J strains. The proposed experiments align with my goals for fellowship training and will allow me the opportunity to gain expertise in high-throughput immune cell profiling, transcriptome analysis, and in vivo approaches to elucidate immune response at the respiratory site. Furthermore, the proposed professional development plan will propel my career goals by enhancing my research independence.

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National Heart Lung and Blood Institute (NHLBI)

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Project Summary/Abstract:  This proposal describes a research plan for Zhengjie Zhou, Ph.D., for the R00 portion of the NIH mentored  career award (K99/R00). The PI is completing training in an NIH K99 fellowship (K99HL166870) and is trained  in vascular biology, lung biology, molecular biology, and bioengineering. This proposal tests the overall  hypothesis of formulating novel lung-targeting nanoparticles to deliver therapeutic mRNA in a cell-specific  manner for the treatment of acute respiratory distress syndrome (ARDS), which is the major cause of death for  severe influenza and SARS-CoV-2 infection. Currently, efficient medicines are still lacking for ARDS therapy.  ARDS is characterized by the dysfunction of endothelial cells (ECs), epithelial cells, and the following  uncontrolled cytokine storm. Based on our recent research about a vascular cell adhesion molecule-1  (VCAM1) targeting nanotherapeutic study, I rationally designed and optimized a targeting lipid nanoparticle  (LNP) that enables robust mRNA delivery in vivo in a cell-specific manner. Leveraging this mRNA delivery  platform, We propose to (i) promote endothelium health by endothelial cell-specific delivery of KLF2 mRNA to  restore KLF2, a transcription factor, that plays a key role in facilitating endothelial health and vasculature  homeostasis. KLF2 was demonstrated significantly reduced in mice lungs induced by LPS, influenza H1N1,  SARS-CoV-2, and COVID-19 patients lungs; (ii) activate epithelial cells innate immune pathway by epithelium specific delivery of 2’-5’-oligoadenylate synthetase 1 (OAS1) mRNA to augment epithelium interferon (IFN)  response through OAS/RNase L pathway to defense respiratory viral infection. Our data demonstrated that  KLF2 mRNA/VCAM1-targeting LNP targeted the inflamed mice lungs endothelium and significantly reduced  the ARDS induced by H1N1. Our preliminary data demonstrated that the OAS1 mRNA/epithelium-targeting  LNP targeted the mice inflamed lung epithelium and significantly reduced the H1N1 replication and lung ARDS.  Aim 1 will comprehensively evaluate the therapeutic potency of VCAM1-targeting LNP to restore endothelial  KLF2 and lessen ARDS in a clinically relevant rat ARDS model induced by high-tidal ventilation (HTV). Aim 2  will determine how epithelium-targeted delivery of OAS1 activates the innate immune response and exerts  antiviral effects in mice by OAS1 mRNA/epithelium-targeting LNP, and will determine its therapeutic effect to  treat respiratory virus-induced ARDS. Successful completion of these projects will provide a promising mRNA  therapeutic treating lung disease and provide an “effective responder” in viral pandemics, regardless of virus  evolution and mutation. This mRNA delivery platform is adaptable and potentially beneficial for various  cardiovascular diseases.

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United States National Institutes of Health