{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:03:34Z","timestamp":1789574614790,"version":"build-2803163510"},"reference-count":54,"publisher":"Cold Spring Harbor Laboratory","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["RNA"],"accepted":{"date-parts":[[2026,7,12]]},"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    MicroRNAs are pivotal regulators of organ and tissue homeostasis and development, and pathogenic mediators of disease. While antagonism of specific microRNA species in vivo is easily accomplished in experimental animal models using locked nucleic acid (LNA)-stabilized antimiRs, microRNA mimicry\u2014that is, increasing the abundance of specific microRNA species\u2014in experimental animals is more challenging. In this study, commercially available naked LNA-stabilized oligonucleotides designed as microRNA mimics were assessed for efficacy in newborn mouse pups, which frequently serve as models for normal human development, or neonatal and pediatric disease. Mimics targeting miR-497a-5p commercially marketed for in vitro or in vivo use were examined for distribution to five organs in developing mouse pups after parenteral administration. Mimics were most effectively delivered to the liver, and in limited instances also to the heart and kidneys, but could not be detected in the brain or lungs. A combination of bulk RNA-seq transcriptomic screening and proteomic screening of liver homogenates revealed that mimics delivered to the liver were functional, either reducing the abundance of the\n                    <jats:italic>Tff3<\/jats:italic>\n                    mRNA transcript, or the abundance of N4bp1 or Mt2 proteins, all of which are cognate targets of miR-497a-5p. Furthermore, the data presented here demonstrate that LNA-stabilized mimics for miR-497a-5p were short-lived in vivo, yet impacted the abundance of both primary and secondary targets of miR-497a-5p albeit with demonstrable hepatotoxicity. This study concludes that while microRNA mimicry using commercially available naked LNA-stabilized oligonucleotides is possible, there remains tremendous scope\u2014and need\u2014for refinement of this technology.\n                  <\/jats:p>","DOI":"10.1261\/rna.081174.126","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:15:21Z","timestamp":1784913321000},"page":"1571-1589","source":"Crossref","is-referenced-by-count":0,"title":["Functional delivery of commercially available microRNA mimics to the organs of developing 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