{"entity": "journal", "iuid": "f6ddc75ef28048a0b2e9f38172d7f499", "timestamp": "2026-07-14T04:21:09.332Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Mol%20Ther%20Nucleic%20Acids.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Mol%20Ther%20Nucleic%20Acids"}}, "title": "Mol Ther Nucleic Acids", "issn": "2162-2531", "issn-l": "2162-2531", "publications_count": 4, "publications": [{"entity": "publication", "iuid": "39cafd188c9e4072bfd89e2955794ce5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/39cafd188c9e4072bfd89e2955794ce5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/39cafd188c9e4072bfd89e2955794ce5"}}, "title": "Immunogenicity and innate immunity to high-dose and repeated vaccination of modified mRNA versus unmodified mRNA.", "authors": [{"family": "Engstrand", "given": "Olivia", "initials": "O"}, {"family": "Joas", "given": "Gustav", "initials": "G"}, {"family": "Miranda", "given": "Marcos C", "initials": "MC"}, {"family": "Yan", "given": "Xianglei", "initials": "X"}, {"family": "Lenart", "given": "Klara", "initials": "K"}, {"family": "Cerveira", "given": "Rodrigo Arcoverde", "initials": "RA"}, {"family": "Reinhardt", "given": "Annika", "initials": "A"}, {"family": "Lor\u00e9", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2025-09-09", "journal": {"title": "Mol Ther Nucleic Acids", "issn": "2162-2531", "volume": "36", "issue": "3", "pages": "102588", "issn-l": "2162-2531"}, "abstract": "mRNA vaccines represent a new era with several novel constructs underway. We compared the responses of high doses and multiple repetitive immunizations of a nucleoside-modified mRNA construct to a sequence-codon-optimized unmodified mRNA construct encoding the identical model antigen (HIV-1 gag). Rhesus macaques were immunized five times at 2-week intervals, with a final boost 20 weeks later. At 24 h post-vaccination, both unmodified (160 \u03bcg) and modified (400 \u03bcg and 800 \u03bcg) mRNA constructs elicited clear but transient increase of plasmacytoid dendritic cells, intermediate CD14+ CD16+ monocytes, and neutrophils along with secretion of type I interferon (IFN)-related and inflammatory cytokines. Unmodified mRNA induced higher interleukin-7 (IL-7) and IFN-\u03b1 levels, whereas modified mRNA induced higher IL-6 levels. Transcriptomic profiling showed significant upregulation of genes related to type I IFN signaling, antigen presentation, and innate immune activation induced by both mRNA constructs. The high-dose modified mRNA induced a higher number of differentially expressed genes at prime, which further increased after the fifth immunization. These differences in innate immune activation nonetheless led to similar levels and kinetics of gag-specific antibody and T cell responses. These findings offer insights into the immunogenic and reactogenic potential of different mRNA vaccine modalities, guiding future vaccine and therapy development.", "doi": "10.1016/j.omtn.2025.102588", "pmid": "40612710", "labels": {"Affinity Proteomics Stockholm": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12221724"}, {"db": "pii", "key": "S2162-2531(25)00142-8"}], "notes": [], "created": "2025-09-19T14:41:12.463Z", "modified": "2025-11-28T14:59:07.787Z"}, {"entity": "publication", "iuid": "73f79f2fc206426caa16aafb578b1761", "links": {"self": {"href": "https://publications.scilifelab.se/publication/73f79f2fc206426caa16aafb578b1761.json"}, "display": {"href": "https://publications.scilifelab.se/publication/73f79f2fc206426caa16aafb578b1761"}}, "title": "CRISPR-Cas9 treatment partially restores amyloid-\u03b2 42/40 in human fibroblasts with the Alzheimer's disease PSEN 1 M146L mutation.", "authors": [{"family": "Konstantinidis", "given": "Evangelos", "initials": "E"}, {"family": "Molisak", "given": "Agnieszka", "initials": "A"}, {"family": "Perrin", "given": "Florian", "initials": "F"}, {"family": "Streubel-Gallasch", "given": "Linn", "initials": "L"}, {"family": "Fayad", "given": "Sarah", "initials": "S"}, {"family": "Kim", "given": "Daniel Y", "initials": "DY"}, {"family": "Petri", "given": "Karl", "initials": "K"}, {"family": "Aryee", "given": "Martin J", "initials": "MJ"}, {"family": "Aguilar", "given": "Ximena", "initials": "X"}, {"family": "Gy\u00f6rgy", "given": "Bence", "initials": "B"}, {"family": "Giedraitis", "given": "Vilmantas", "initials": "V"}, {"family": "Joung", "given": "J Keith", "initials": "JK"}, {"family": "Pattanayak", "given": "Vikram", "initials": "V"}, {"family": "Essand", "given": "Magnus", "initials": "M"}, {"family": "Erlandsson", "given": "Anna", "initials": "A"}, {"family": "Berezovska", "given": "Oksana", "initials": "O"}, {"family": "Ingelsson", "given": "Martin", "initials": "M"}], "type": "journal article", "published": "2022-06-14", "journal": {"title": "Mol Ther Nucleic Acids", "issn": "2162-2531", "volume": "28", "pages": "450-461", "issn-l": "2162-2531"}, "abstract": "Presenilin 1 (PS1) is a central component of \u03b3-secretase, an enzymatic complex involved in the generation of the amyloid-\u03b2 (A\u03b2) peptide that deposits as plaques in the Alzheimer's disease (AD) brain. The M146L mutation in the PS1 gene (PSEN1) leads to an autosomal dominant form of early-onset AD by promoting a relative increase in the generation of the more aggregation-prone A\u03b242. This change is evident not only in the brain but also in peripheral cells of mutation carriers. In this study we used the CRISPR-Cas9 system from Streptococcus pyogenes to selectively disrupt the PSEN1 allele in human fibroblasts. A disruption of more than 50% of mutant alleles was observed in all CRISPR-Cas9-treated samples, resulting in reduced extracellular A\u03b242/40 ratios. Fluorescence resonance energy transfer-based conformation and western blot analyses indicated that CRISPR-Cas9 treatment also affects the overall PS1 conformation and reduces PS1 levels. Moreover, our guide RNA did not lead to any detectable editing at the highest-ranking candidate off-target sites identified by ONE-seq and CIRCLE-seq. Overall, our data support the effectiveness of CRISPR-Cas9 in selectively targeting the M146LPSEN1 allele and counteracting the AD-associated phenotype. We believe that this system could be developed into a therapeutic strategy for patients with this and other dominant mutations leading to early-onset AD.M146L", "doi": "10.1016/j.omtn.2022.03.022", "pmid": "35505961", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9043867"}, {"db": "pii", "key": "S2162-2531(22)00071-3"}], "notes": [], "created": "2022-11-28T10:49:45.806Z", "modified": "2022-11-28T10:49:45.810Z"}, {"entity": "publication", "iuid": "2fb641f0015d4cf68ee3a07d329f2564", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2fb641f0015d4cf68ee3a07d329f2564.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2fb641f0015d4cf68ee3a07d329f2564"}}, "title": "Comprehensive RNA sequencing analysis in serum and muscle reveals novel small RNA signatures with biomarker potential for Duchenne Muscular Dystrophy", "authors": [{"family": "Coenen-Stass", "given": "Anna M L", "initials": "AML"}, {"family": "Sork", "given": "Helena", "initials": "H"}, {"family": "Gatto", "given": "Sole", "initials": "S"}, {"family": "Godfrey", "given": "Caroline", "initials": "C"}, {"family": "Bhomra", "given": "Amarjit", "initials": "A"}, {"family": "Krjut\u0161kov", "given": "Kaarel", "initials": "K"}, {"family": "Hart", "given": "Jonathan R", "initials": "JR"}, {"family": "Westholm", "given": "Jakub O", "initials": "JO"}, {"family": "O\u2019Donovan", "given": "Liz", "initials": "L"}, {"family": "Roos", "given": "Andreas", "initials": "A"}, {"family": "Lochm\u00fcller", "given": "Hanns", "initials": "H"}, {"family": "Puri", "given": "Pier Lorenzo", "initials": "PL"}, {"family": "Andaloussi", "given": "Samir EL", "initials": "SE"}, {"family": "Wood", "given": "Matthew J A", "initials": "MJA"}, {"family": "Roberts", "given": "Thomas C", "initials": "TC"}], "type": "journal-article", "published": "2018-08-00", "journal": {"volume": null, "issn": "2162-2531", "issue": null, "pages": null, "title": "Mol Ther Nucleic Acids", "issn-l": "2162-2531"}, "abstract": "Extracellular small RNAs (sRNAs), including microRNAs (miRNAs), are promising biomarkers for diseases such as Duchenne muscular dystrophy (DMD), although their biological relevance is largely unknown. To investigate the relationship between intracellular and extracellular sRNA levels on a global scale, we performed sRNA sequencing in four muscle types and serum from wild-type, dystrophic mdx, and mdx mice in which dystrophin protein expression was restored by exon skipping. Differentially abundant sRNAs were identified in serum (mapping to miRNA, small nuclear RNA [snRNA], and PIWI-interacting RNA [piRNA] loci). One novel candidate biomarker, miR-483, was increased in both mdx serum and muscle, and also elevated in DMD patient sera. Dystrophin restoration induced global shifts in miRNA (including miR-483) and snRNA-fragment abundance toward wild-type levels. Specific serum piRNA-like sRNAs also responded to exon skipping therapy. Absolute miRNA expression in muscle was positively correlated with abundance in the circulation, although multiple highly expressed miRNAs in muscle were not elevated in mdx serum, suggesting that both passive and selective release mechanisms contribute to serum miRNA levels. In conclusion, this study has revealed new insights into the sRNA biology of dystrophin deficiency and identified novel DMD biomarkers.", "doi": "10.1016/j.omtn.2018.08.005", "pmid": "30219269", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "SRA", "description": "https://trace.ncbi.nlm.nih.gov/Traces/sra/?study=SRP102619", "key": "SRP102619"}], "notes": [], "created": "2018-08-21T11:12:55.111Z", "modified": "2024-01-16T13:48:45.897Z"}, {"entity": "publication", "iuid": "1bc6175eacc84744aafca007e4d5f81a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1bc6175eacc84744aafca007e4d5f81a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1bc6175eacc84744aafca007e4d5f81a"}}, "title": "Expression analysis in multiple muscle groups and serum reveals complexity in the microRNA transcriptome of the mdx mouse with implications for therapy.", "authors": [{"family": "Roberts", "given": "Thomas C", "initials": "TC"}, {"family": "Blomberg", "given": "K Emelie M", "initials": "KE"}, {"family": "McClorey", "given": "Graham", "initials": "G"}, {"family": "El Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Godfrey", "given": "Caroline", "initials": "C"}, {"family": "Betts", "given": "Corinne", "initials": "C"}, {"family": "Coursindel", "given": "Thibault", "initials": "T"}, {"family": "Gait", "given": "Michael J", "initials": "MJ"}, {"family": "Smith", "given": "C I Edvard", "initials": "CI"}, {"family": "Wood", "given": "Matthew J A", "initials": "MJ"}], "type": "journal article", "published": "2012-08-14", "journal": {"volume": "1", "issn": "2162-2531", "issue": null, "pages": "e39", "title": "Mol Ther Nucleic Acids", "issn-l": "2162-2531"}, "abstract": "MicroRNAs (miRNAs) are a class of small RNAs that regulate gene expression and are implicated in wide-ranging cellular processes and pathological conditions including Duchenne muscular dystrophy (DMD). We have compared differential miRNA expression in proximal and distal limb muscles, diaphragm, heart and serum in the mdx mouse relative to wild-type controls. Global transcriptome analysis revealed muscle-specific patterns of differential miRNA expression as well as a number of changes common between tissues, including previously identified dystromirs. In the case of miR-31 and miR-34c, upregulation of primary-miRNA transcripts, precursor hairpins and all mature miRNAs derived from the same transcript or miRNA cluster, strongly suggests transcriptional regulation of these miRNAs. The most striking differences in differential miRNA expression were between muscle tissue and serum. Specifically, miR-1, miR-133a, and miR-206 were highly abundant in mdx serum but downregulated or modestly upregulated in muscle, suggesting that these miRNAs are promising disease biomarkers. Indeed, the relative serum levels of these miRNAs were normalized in response to peptide-phosphorodiamidate morpholino oligonucleotide (PMO) mediated dystrophin restoration therapy. This study has revealed further complexity in the miRNA transcriptome of the mdx mouse, an understanding of which will be valuable in the development of novel therapeutics and for monitoring their efficacy.", "doi": "10.1038/mtna.2012.26", "pmid": "23344181", "labels": {"Bioinformatics and Expression Analysis (BEA)": null}, "xrefs": [{"db": "pii", "key": "mtna201226"}, {"db": "pmc", "key": "PMC3437806"}], "notes": [], "created": "2017-05-04T15:03:13.026Z", "modified": "2017-05-30T14:50:53.146Z"}], "created": "2017-05-09T09:12:26.945Z", "modified": "2020-11-27T13:14:09.348Z"}