GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE319nnn/GSE319608/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE319608GEOGSEfalseEnhanced antisense oligonucleotide delivery reveals that transcript turnover impacts apparent splicing rescue in myotonic dystrophySteric-blocking antisense oligonucleotides rescue Myotonic dystrophy type 1 phenotypes in preclinical models and are under evaluation in clinical trials. However, rationale for biomarker selection remains a topic of debate. Here, we show that a cyclic cell-penetrating peptide that escapes endosomes enhances muscle delivery of a phosphorodiamidate morpholino oligonucleotide (PMO) designed to block pathogenic CUG repeat expansions in HSALR mice. A single systemic administration rescued mis-splicing and eliminated myotonia one-week post-injection, with partial splicing rescue evident after 24 hours. Interestingly, some exons showed more robust rescue than others, but relationships between MBNL concentration ([MBNL]) and Percent Spliced In (Ψ) could not fully explain extent of rescue. We hypothesized that since pre-existing transcripts must be degraded to reveal full drug effect, rates of transcript replacement might account for these discrepancies. We formulated a mathematical framework and used Bayesian inference to model how apparent Ψ lags behind nascent Ψ as a function of time; faster rates of replacement result in shorter lags. In vivo 5-ethynyl uridine labeling followed by RNAseq validated these predictions. Overall, we show that transcript turnover influences Ψ during periods of dynamically changing [MBNL] and recommend that this be considered when selecting splicing biomarkers and interpreting responses to therapeutic interventions.2026/05/28GSE319608GSM9521198GSM9521231GSM9521199GSM9521232GSM9521233GSM9521234GSM9521194GSM9521195GSM9521196GSM9521230GSM9521197GSM9521239GSM9521235GSM9521236GSM9521237GSM9521238GSM9521190GSM9521191GSM9521192GSM9521193GSM9521242GSM9521243GSM9521244GSM9521245GSM9521240GSM9521241GSM9521246GSM9521247GSM9521248GSM9521249GSM9521176GSM9521210GSM9521177GSM9521211GSM9521178GSM9521179GSM9521212GSM9521172GSM9521173GSM9521174GSM9521175GSM9521217GSM9521218GSM9521219GSM9521213GSM9521214GSM9521215GSM9521216GSM9521170GSM9521171GSM9521187GSM9521220GSM9521188GSM9521221GSM9521222GSM9521189GSM9521223GSM9521183GSM9521184GSM9521185GSM9521186GSM9521228GSM9521229GSM9521224GSM9521225GSM9521226GSM9521227GSM9521180GSM9521181GSM9521182GSM9521154GSM9521155GSM9521156GSM9521157GSM9521158GSM9521159GSM9521165GSM9521166GSM9521167GSM9521200GSM9521201GSM9521168GSM9521161GSM9521162GSM9521163GSM9521164GSM9521206GSM9521207GSM9521208GSM9521209GSM9521202GSM9521169GSM9521203GSM9521204GSM9521205GSM9521160GSM9521250GSM952125130172319608Mus musculus[42163456]