Biology subjects

Alameh, M.-G.

Publications and source records attributed to Alameh, M.-G..

At least 19 recordsLinked to original sources

bioRxiv2026

Impact of RNA modification and IL-12 boosts on mRNA-LNP vaccine-elicited CD8+ T cell responses

Development of effective HIV-1 vaccines requires strategies for inducing both CD8+ T cell and neutralizing antibody responses. Nucleoside-modified mRNA-lipid-nanoparticles (LNP) induce more potent antibody responses than unmodified mRNA-LNP vaccines, while unmodified mRNA is typically employed for CD8+ T cell-inducing vaccines. Here, we compared the abilities of differing ratios of unmodified versus modified mRNA expressing a SIV conserved-region CD8+ T cell immunogen co-administered with IL-12-encoding mRNA-LNP during boosting to induce CD8+ T cell and humoral responses in non-human primates, assessing responses in ChAdOx1-primed controls in parallel. Serial priming and boosting with fully-unmodified mRNA elicited higher-magnitude, more CD8-biased T cell responses than fully-modified mRNA, that were durably maintained after the IL-12-encoding mRNA boosts. Inclusion of 30% nucleoside-modified mRNA enhanced antibody titers, suggesting potential benefits to a mixed-composition vaccine.

immunology↗

bioRxiv2026

Immunotherapy restores therapeutic efficacy of fecal microbiome transplants to treat Clostridioides difficile

Microbiome-based therapeutics to treat enteric bacterial infections requires stable engraftment of transplanted beneficial bacteria that target and eliminate the pathogen. The host factors that determine whether a microbiome transplant engrafts remain largely unresolved. Here we demonstrate that Interleukin-10 (IL-10) signaling deficiency leads to impaired fecal microbiota transplantation (FMT) engraftment and failure to resolve Clostridioides difficile infection in mice. In the absence of IL-10-mediated immunoregulation provided by Foxp3+ Treg cells, increased IFN-{gamma} signaling in the intestine leads to elevated production of reactive oxygen/nitrogen species (ROS/RNS) by neutrophils and epithelial cells that supports the growth of inflammation-tolerant microbes, inhibits FMT engraftment, and impairs resolution of C. difficile. FMT treatment success can be restored by antibody-mediated blockade of IFN-{gamma} signaling, neutrophil depletion or inhibition of ROS/RNS production. Lastly, we developed an Il10-mRNA-LNP immunotherapy to boost IL-10 signaling in FMT Non-Responsive mice and demonstrate that Il10-mRNA-LNP administration is sufficient to restore FMT engraftment and subsequent resolution of C. difficile. Combined, these data support a mechanism by which IL-10 released by Treg cells limits IFN-{gamma} mediated intestinal inflammation thereby promoting an intestinal microenvironment receptive to FMT engraftment and resolution of C. difficile. These data demonstrate that the host's immune status can be therapeutically modulated to improve microbiome-based approaches to treat infection.

immunology↗

bioRxiv2026

Protective pan-betacoronavirus neutralizing antibodies by vaccination

The continued emergence of betacoronaviruses underscores the urgent need for vaccines that provide broadly protective immunity. Here, we present an epitope-focused vaccine strategy targeting the conserved S2 stem-helix region of the spike fusion machinery, a broadly neutralizing antibody-(bnAb) epitope shared across betacoronaviruses yet partially occluded on the native spike. Immunization of non-human primates with engineered S2 stem-helix nanoparticle immunogens, alone or followed by a SARS-CoV-2 BA.1 spike mRNA boost, elicited broadly cross-reactive antibody responses against sarbecoviruses, merbecoviruses, and embecoviruses and neutralized SARS-CoV-2, multiple variants, other sarbecoviruses, and MERS-CoV. Vaccine-elicited monoclonal antibodies displayed broad in-vitro neutralizing activity and protected against both SARS-CoV-2 and MERS-CoV in-vivo. Structural analyses revealed conserved features between rhesus and human stem-helix bnAbs, supporting the translational potential. Overall, our findings provide proof-of-concept that epitope-focused nanoparticle immunogens can target partially occluded, immunoquiescent bnAb epitopes, laying the groundwork for pan-betacoronavirus vaccines that provide broad protection and strengthen pandemic preparedness. ONE SENTENCE SUMMARYEpitope-focused S2 stem-helix nanoparticle immunogens elicit protective broadly neutralizing antibodies (bnAbs) against diverse betacoronaviruses in non-human primates, establishing a framework for development of pan-betacoronavirus vaccines.

immunology↗

bioRxiv2026

Adenosine deaminase co-immunization reverses age-associated immunosenescence by restoring germinal center T follicular helper cell function

Older adults experience disproportionate morbidity and mortality from Clostridioides difficile infection (CDI); however, existing toxoid- and receptor binding domain (RBD)-based vaccines elicit suboptimal protection in aged hosts due to the age-associated defects in CD4+ T cell function, T follicular helper (TFH) cell activation, and antibody quality. We evaluated whether adenosine deaminase (ADA), an enzymatic immune modulator that degrades immunosuppressive adenosine, and improves GC TFH differentiation and survival, could reverse these age-related impairments when co-delivered with DNA vaccine plasmids targeting toxin A and B RBDs (pRBD). In aged mice, pRBD vaccination alone produced markedly reduced toxin-specific effector/memory CD4+ T cells, diminished TFH activation, and poor toxin A neutralization compared to vaccinated young mice. Co-immunization with plasmid-encoded adenosine deaminase-1 (pADA) restored toxin-specific CD4+ T cell generation and cytokine production, activation-induced marker (AIM) TFH responses, and antibody-mediate toxin neutralization to levels comparable to young adults. Mechanistically, pADA co-immunization was associated with the reduction of CXCR4 on germinal center (GC) TFH cells--an age-related defect linked to impaired GC positioning and diminished B cell help--suggesting that ADA improves humoral quality by correcting GC TFH mislocalization. These immune enhancements corresponded with improved clinical outcomes in morbidity, mortality, and weight-loss following C. difficile spore challenge of aged mice. Finally, pADA significantly reduced adenosine levels in aged lymph nodes, implicating a potential enzymatic-based regulation of GC immunosenescence. Together, these findings identify ADA as a metabolic adjuvant capable of reversing key features of vaccine immunosenescence and highlight adenosine dependent CXCR4 regulation as a tractable axis for improving vaccine efficacy in older populations.

immunology↗

bioRxiv2026

Correction of a recurrent pathogenic variant in methylmalonic acidemia using adenine base editing

Methylmalonic acidemia (MMA) is a recessive genetic disease caused by variants in the MMUT (mitochondrial enzyme methylmalonyl-CoA mutase) gene or by defects in transport or metabolism of MMUT cofactor (5 deoxyadenosylcobalamin), including variants in the MMAB gene. For the most recurrent pathogenic MMAB variant, c.556C>T (R186W), we identified a corrective editing strategy using adenine base editing. Deploying an adenine base editor mRNA and optimized hybrid guide RNA with lipid nanoparticles, we observed efficient in vitro corrective editing of the variant to wild-type, with minimized bystander editing and off-target editing in hepatocytes. These observations lay the groundwork for a gene editing therapy for patients with MMA resulting from at least one copy of the MMAB c.556C>T (R186W) variant, as well as a platform of similar therapies for patients with MMA caused by other variants amenable to adenine base editing.

genetics↗

bioRxiv2026

Evaluation of an H5 influenza virus mRNA-lipid nanoparticle (LNP) vaccine in lactating dairy cows

Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5N1 virus has recently emerged in dairy cattle in the United States. The virus replicates primarily in the mammary gland of infected cattle, leading to dramatic reductions in milk production. It is thought that the virus transmits from animal to animal through viral shedding in milk, and therefore, vaccines that decrease the amount of virus in milk can potentially limit the current outbreak and reduce the risk of H5N1 spillover into humans. Here, we assess the immunogenicity and efficacy of a clade 2.3.4.4b H5 mRNA-LNP vaccine in lactating dairy cows. We found that the H5 mRNA-LNP vaccine elicited robust antibody responses in sera and milk and significantly reduced viral replication and disease caused by clade 2.3.4.4b H5N1 intramammary infection.

microbiology↗

bioRxiv2026

Generation and characterization of a novel MHC-II tetramer for tracking and characterization of toxin B-specific CD4+ T cell responses

The gastrointestinal pathogen Clostridioides difficile, is a major burden for health systems due to high rates of recurrence. C. difficile pathogenesis is mediated by two virulence factors, toxin A (TcdA) and Toxin B (TcdB). Antibodies specific for TcdA and TcdB are correlated with protection from symptomatic recurrence, however, the role for CD4+ T cells is poorly understood in part due to the lack of tools to study the toxin-specific CD4+ T cell response. Our group recently demonstrated the antibody and CD4+ T cell response to C. difficile toxins is impaired via the glucosyltransferase activity of the toxins; however, tools do not exist to study the protective capacity and the phenotype of toxin-specific CD4+ T cells. Therefore, we developed an MHC-II tetramer to identify TcdB-specific CD4+ T cells via flow cytometry. Herein, we identified an immunodominant epitope (TcdB1961-1975) in the CROPs region of TcdB and optimized an MHC-II tetramer for use in tracking and phenotyping TcdB-specific CD4+ T cell responses following multiple different immunization strategies in mice. Utilizing the tetramer, TcdB-specific T follicular helper (Tfh) cells were detected following TcdB-CROPs mRNA-LNP vaccination validating the advantage of the tetramer. Furthermore, using a modular mRNA vector expressing the TcdB1961 peptide covalently bound to the beta chain of MHC-II (MHC-II{beta}) we were able to generate a robust population of TcdB-specific CD4+ T cells. These data outline the generation of new tools for the C. difficile field and lay the groundwork for future studies of toxin-specific CD4+ T cell responses.

immunology↗

bioRxiv2026

Rapid Assessment of Immune Effector Cell-mediated Cytotoxicity using mRNA Lipid Nanoparticles

Cellular immunotherapy has revolutionized cancer treatment by enabling more targeted and personalized disease management. As the field progresses, there is an increasing need for high-throughput in vitro assays to efficiently assess the cytotoxicity of therapeutic cells. Conventional cytotoxicity assays pose various limitations in the workflow and scalability. Here, we present an mRNA lipid nanoparticle (mRNA-LNP) approach to efficiently and robustly deliver reporter genes to target cells for assessing immune effector cell-mediated cytotoxicity. This approach enables the rapid, homogenous reporter expression without compromising the viability of target cells. The cytotoxicity results obtained using mRNA-LNP-transfected cells are highly consistent and comparable to those obtained using cell lines with stable reporter gene expression. Finally, we highlight the mRNA-LNP approachs compatibility across a diverse range of tumor models, including primary tumor-derived models, enabling rapid and high-throughput assessment of the potency of various cytotoxic therapeutic cells.

immunology↗

bioRxiv2025

Lipid nanoparticle co-delivery of mRNA and a small molecule drug for oral cancer chemoimmunotherapy

Oral squamous cell carcinoma (OSCC) represents 90% of all head and neck cancers. Despite decades of research, the 5-year survival rate is 50%, and strikingly, the overall incidence rate is projected to increase by 30% in the next ten years, which will result in a sharp increase in mortality. Two fundamental aspects of OSCC are that it progresses via the inactivation and mutation of tumor suppressor (TS) genes and has a "cold" tumor immune microenvironment (TIME). A major barrier in the treatment of OSCC is the lack of novel therapies clinicians have at their disposal that are designed to disrupt tumor progression by reshaping the cold tumors into inflammatory "hot" tumors. To overcome these obstacles, we employed a lipid nanoparticle (LNP) that co-encapsulates p53 mRNA and the small molecule ciclopirox (CPX). We demonstrate that both drugs have innate chemotherapeutic properties by facilitating caspase activation. Moreover, these therapies can create a less immunosuppressive TIME in part by repolarizing tumor-associated macrophages (TAMs) to M1-like phenotypes. When formulated together, our platform provides an all-in-one approach for OSCC, effective in both p53-therapy-susceptible and p53-therapy-resistant models. Additionally, this work provides a template for a delivery platform capable of tackling multiple mechanisms of OSCC progression and survival.

bioengineering↗

bioRxiv2025

Clostridioides difficile toxin A and toxin B inhibit toxin-specific adaptive immune responses through glucosyltransferase-dependent activity

Clostridioides difficile colonizes the gastrointestinal tract and secretes two virulence factors: toxin A (TcdA) and toxin B (TcdB). Protective immunity against C. difficile infection is limited as patients are susceptible to multiple rounds of recurrent infections. The factors determining whether immunity to TcdA and TcdB is generated remain incompletely defined. We determined that C. difficile-infected mice generate antibody and IL-17A-producing CD4+ T cell responses to TcdA, but not TcdB. To determine the mechanism of the failed anti-TcdB immunity, C. difficile mutant strains expressing glucosyltransferase inactive (GTX) TcdA, and/or glucosyltransferase inactive TcdB were used. Infection with TcdBGTX or dual mutant (TcdAGTX TcdBGTX) restored TcdB-specific antibody responses, while infection with TcdAGTX or TcdAGTX TcdBGTX led to an earlier induction of TcdA-specific antibodies. Finally, infection with the dual GTX mutant enhanced TcdA and TcdB-specific CD4+ T cell responses. These data demonstrate that the glucosyltransferase activity of TcdA and TcdB hinders the antigen-specific adaptive immune response to itself and may be a mechanism that underlies high recurrence rates following C. difficile infection in patients.

immunology↗

bioRxiv2025

Investigating the Impact of Hypoxia and Syncytialization on Lipid Nanoparticle-Mediated mRNA Delivery to Placental Cells

Placental dysfunction leads to pregnancy-related disorders that affect up to 15% of pregnancies. Several of these, such as preeclampsia, are symptomatically managed but have no curative treatments other than preterm delivery. Placental dysfunction arises from improper placental development, leading to restricted blood vessel formation and a hypoxic placental microenvironment. The development of placental therapeutics is challenging due to the complex physiology that enables the placenta to have precise control over endocytosis and transport. Here, we use a simple culture system that combines hypoxia and trophoblast syncytialization to model the functional syncytiotrophoblast layer of the placenta under hypoxic stress. Using this model, we evaluate the impact of hypoxia on lipid nanoparticle (LNP)-mediated mRNA delivery. Our data shows that hypoxia hinders syncytiotrophoblast formation in vitro. Despite this, LNP delivery to syncytiotrophoblasts increases protein translation and secretion, particularly under hypoxic conditions. Further, we show delivery of a therapeutic mRNA, placental growth factor (PlGF), to syncytiotrophoblasts in hypoxia, which restored diminished PlGF levels back to normoxic controls. These findings provide an LNP platform for efficient mRNA delivery to hypoxic trophoblasts and demonstrate the importance of considering hypoxia towards the development of drug delivery platforms for placental therapeutics. Translational Impact StatementThis study investigates lipid nanoparticle (LNP)-mediated mRNA delivery to placental cells cultured in a simple hypoxia model, simulating the microenvironment of the placenta during pregnancy complications such as preeclampsia. We provide insights essential for developing LNP drug delivery platforms for treating disorders of the placenta. These findings will guide future design of LNP-based treatments for delivery to the diseased, hypoxic placenta, minimizing systemic exposure and improving outcomes in maternal and fetal health for conditions lacking effective, targeted interventions.

bioengineering↗

bioRxiv2025

Bioinspired Oxidized mRNA Lipid Nanoparticles for Ex Vivo Engineering of Chimeric Antigen Receptor Macrophages Targeting Solid Tumors

Solid tumors remain difficult to treat via conventional and novel therapeutic strategies. Immunotherapies such as chimeric antigen receptor T (CAR-T) cell therapy have been remarkably effective in treating hematological cancers, but their efficacy is limited in solid tumors. Recently, CAR macrophages (CAR-Ms) have emerged as a promising solid tumor immunotherapy, primarily for their intrinsic tumor infiltration and effector functions. However, CAR-Ms are engineered using viral transduction, which is associated with aberrant immunogenicity and toxicity. To overcome these challenges, we developed a bioinspired oxidized lipid nanoparticle (LNP) platform for mRNA-based engineering of human CAR-Ms. A library of 24 ionizable lipids was synthesized, formulated into LNPs, and screened for delivery to human macrophages. The composition of the top LNP was subsequently optimized using an orthogonal design of experiments (DoE) and physicochemical properties, such as size and mRNA encapsulation, were tuned via optimization of microfluidic mixing parameters, yielding a particle that significantly outperformed a gold standard C12-200 LNP. Utilizing small molecule and antibody inhibitors, we demonstrate that uptake of optimized LNPs into macrophages is driven by apolipoprotein E (ApoE) independent macropinocytosis, which is further supported by potent extrahepatic spleen tropism upon intravenous administration to mice. Lastly, we demonstrate the translatability of this LNP platform and utilize it to engineer functional primary human HER2-CAR-Ms ex vivo with potent antigen-specific tumor killing, validated in an ex vivo co-culture with ovarian cancer cells. This bioinspired oxidized LNP platform can potentially be utilized to engineer a range of human CAR-M immunotherapies to treat various types of solid tumors.

bioengineering↗

bioRxiv2025

Plug-and-play assembly of biodegradable ionizable lipids for potent mRNA delivery and gene editing in vivo

mRNA-based gene editing therapeutics offer the potential to permanently cure diseases but are hindered by suboptimal delivery platforms. Here, we devise a robust combinatorial chemistry for plug-and-play assembly of diverse biodegradable ionizable lipids and identify a lead candidate that produces superior lipid nanoparticles for various gene editing tools delivery in vivo. Our study highlights the utility of this synthetic approach and the generality of this platform for potent in vivo gene editing.

bioengineering↗

bioRxiv2025

Cytokine mRNA Delivery and Local Immunomodulation in the Placenta using Lipid Nanoparticles

During pregnancy, the maternal immune system adapts to balance tolerance of the semi-allogenic fetus while protecting the fetus from pathogens. Dysregulated immune activity at the maternal-fetal interface contributes to pregnancy complications, such as recurrent pregnancy loss and preeclampsia. Compared to healthy placentas, preeclamptic placentas exhibit increased pro-inflammatory signaling, including a predominance of inflammatory macrophages, leading to impaired tissue remodeling and restricted blood flow. However, the precise mechanisms driving this immune imbalance remain poorly understood, in part due to the lack of tools to probe individual pathways. Here, we use lipid nanoparticles (LNPs) to deliver cytokine-encoded mRNA to placental cells, called trophoblasts, enabling local immunomodulation. LNP-mediated delivery of IL-4 and IL-13 mRNA induced cytokine secretion by trophoblasts, leading to polarization of primary human monocytes toward anti-inflammatory phenotypes. Notably, lowering the mRNA dose increased expression of alternatively-activated macrophage markers, revealing an inverse relationship between dose and polarization status. Intravenous injection of LNPs in pregnant mice achieved placental secretion of IL-4 and IL-13 with minimal changes to pro-inflammatory cytokines in the serum. These findings establish LNPs as a tool for local immunomodulation in the placenta, offering a strategy to study and treat immune dysfunction in pregnancy and in other inflammatory conditions.

bioengineering↗

bioRxiv2025

The type I IFN-IL-27 axis promotes mRNA vaccine-induced CD8+ T cell responses

The ability of lipid nanoparticle (LNP)-delivered mRNA vaccines to induce type I IFNs is critical to promote CD8+ T cell responses. The studies presented here indicate that immunization with nucleoside modified mRNA-LNP vaccines drives myeloid cell expression of the cytokine IL-27, which acts on antigen-specific CD8+ T cells to sustain T cell expansion. In vitro and in vivo studies revealed that type I IFN signaling is necessary for mRNA-LNP-induced IL-27 production, that immunization failed in IL-27 KO mice, and that immunization of IFNAR1-deficient mice with mRNA-LNP particles that also encode IL-27 mRNA restored antigen-specific CD8+ T cell responses. In addition, IL-27 mRNA-LNPs served as an adjuvant that improved cytolytic CD8+ T cell responses and the therapeutic efficacy of mRNA-LNPs to drive anti-pathogen and anti-tumor immunity. These studies highlight the central role of IL-27 in mRNA-LNP induced CD8+ T cell responses and the ability of this cytokine to augment the functionality of the CD8+ T cell response for prophylactic or therapeutic immunization.

immunology↗

bioRxiv2024

An IL-12 mRNA-LNP adjuvant enhances mRNA-LNP vaccine induced CD8+ T cell responses

The design of vaccines that induce CD8+ T cell responses has historically been a challenge, but the development of viral vectors or lipid nanoparticles (LNPs) to deliver mRNA that encode for target antigens provide more effective strategies to generate protective CD8+ T cell memory. Because interleukin-12 (IL-12) supports CD8+ T cell expansion and acquisition of effector functions, studies were performed to assess its contribution to the ability of an mRNA vaccine to promote CD8+ T cell responses. In vitro and in vivo, mRNA-LNPs did not stimulate myeloid cell production of IL-12, and the CD8+ T cell response to vaccination with the model antigen ovalbumin (OVA) was IL-12 independent. However, co-administration of IL-12 mRNA-LNPs with OVA mRNA-LNPs enhanced OVA-specific CD8+ T cell expansion, improved acquisition of effector function and resulted in an expanded memory CD8+ T cell pool. These heightened responses were associated with improved protective responses against Listeria monocytogenes-OVA and B16 FO-OVA melanoma. Thus, modification of mRNA vaccine formulations by inclusion of a cytokine mRNA provides a strategy to enhance CD8+ T cell mediated protection.

immunology↗

bioRxiv2024

Improved specificity and efficacy of base-editing therapies with hybrid guide RNAs

Phenylketonuria (PKU), pseudoxanthoma elasticum (PXE), and hereditary tyrosinemia type 1 (HT1) are autosomal recessive disorders linked to the PAH, ABCC6, and FAH and HPD genes, respectively. Here we evaluated the off-target editing profiles of clinical lead guide RNAs (gRNAs) that, when combined with adenine base editors (ABEs), correct the recurrent PAH P281L variant, PAH R408W variant, or ABCC6 R1164X variant or disrupt either of two sites in the HPD gene (a modifier gene of HT1) in human hepatocytes. To mitigate off-target mutagenesis, we systematically screened hybrid gRNAs with DNA nucleotide substitutions. Comprehensive and variant-aware specificity profiling of these hybrid gRNAs revealed dramatically reduced off-target editing and reduced bystander editing in cells. In humanized PAH P281L and ABCC6 R1164X mouse models of PKU and PXE, we showed that when formulated in lipid nanoparticles (LNPs) with ABE mRNA, selected hybrid gRNAs reverted disease phenotypes, reduced off-target editing, increased on-target editing, and reduced bystander editing in vivo. These studies highlight the utility of hybrid gRNAs to improve the safety and efficiency of adenine base editing therapies.

molecular biology↗

bioRxiv2023

Targeting lipid nanoparticles to the blood brain barrier to ameliorate acute ischemic stroke

After more than 100 failed drug trials for acute ischemic stroke (AIS), one of the most commonly cited reasons for the failure has been that drugs achieve very low concentrations in the at-risk penumbra. To address this problem, here we employ nanotechnology to significantly enhance drug concentration in the penumbras blood-brain barrier (BBB), whose increased permeability in AIS has long been hypothesized to kill neurons by exposing them to toxic plasma proteins. To devise drug-loaded nanocarriers targeted to the BBB, we conjugated them with antibodies that bind to various cell adhesion molecules on the BBB endothelium. In the transient middle cerebral artery occlusion (tMCAO) mouse model, nanocarriers targeted with VCAM antibodies achieved the highest level of brain delivery, nearly 2 orders of magnitude higher than untargeted ones. VCAM-targeted lipid nanoparticles loaded with either a small molecule drug (dexamethasone) or mRNA (encoding IL-10) reduced cerebral infarct volume by 35% or 73%, respectively, and both significantly lowered mortality rates. In contrast, the drugs delivered without the nanocarriers had no effect on AIS outcomes. Thus, VCAM-targeted lipid nanoparticles represent a new platform for strongly concentrating drugs within the compromised BBB of penumbra, thereby ameliorating AIS. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/544645v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@86762dorg.highwire.dtl.DTLVardef@1b89a2aorg.highwire.dtl.DTLVardef@916d85org.highwire.dtl.DTLVardef@1ad4670_HPS_FORMAT_FIGEXP M_FIG C_FIG Acute ischemic stroke induces upregulation of VCAM. We specifically targeted upregulated VCAM in the injured region of the brain with drug- or mRNA-loaded targeted nanocarriers. Nanocarriers targeted with VCAM antibodies achieved the highest brain delivery, nearly orders of magnitude higher than untargeted ones. VCAM-targeted nanocarriers loaded with dexamethasone and mRNA encoding IL-10 reduced infarct volume by 35% and 73%, respectively, and improved survival rates.

pharmacology and toxicology↗