{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T21:44:26Z","timestamp":1784238266546,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Despite advances in the fields of lipoplexes, metal nanoparticles, and other nucleic acid carriers, intracellular delivery of DNA\/RNA therapeutics remains a pressing area of molecular medicine. The existing delivery systems have limitations in terms of stability, efficacy, or toxicity. Peptide-based coacervates have recently emerged as a promising alternative. They offer several advantages, including easy DNA\/RNA incorporation, low toxicity, and the ability to penetrate membranes. However, they have one main drawback: inefficient intracellular unpacking. In this study, we present a novel approach to programmed drug release from peptide-based coacervates. We used a previously described intrinsically disordered histidine-rich peptide as a coacervate scaffold and introduced a viral or human protein-derived ATP-responsive module into its sequence. We assembled the coacervates by mixing the resulting peptides with RNA and a model oligonucleotide (ODN), plasmid DNA, or mRNA in a pseudophysiological buffer. The admixtures of labeled peptides and ODN enabled monitoring coacervate formation and dynamics using fluorescence microscopy. The coacervates were relatively stable in ATP-free environments and underwent rearrangements involving the partial release of the ODN in the presence of ATP. The coacervates penetrated HEK293 cells within 4 hours and released the ODN into the cytoplasm within 20 h. They were inferior to the ATP-insensitive (control) peptide in delivery assays with plasmid DNA and mRNA but outperformed the control peptide in assays with the ODN. Our preliminary results suggest that ATP-sensitive coacervates have potential as ODN carriers.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1767656","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:22:09Z","timestamp":1770960129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["ATP-sensitive peptide-based coacervates for intracellular delivery of therapeutic oligonucleotides"],"prefix":"10.3389","volume":"13","author":[{"given":"Tatiana","family":"Vedekhina","sequence":"first","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]},{"name":"MIREA\u2013Russian Technological University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Anufriev","sequence":"additional","affiliation":[{"name":"University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Polischuk","sequence":"additional","affiliation":[{"name":"Lomonosov Moscow State University","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta","family":"Malakhova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Alieva","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viacheslav","family":"Severov","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Bogomiakova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Bobrovsky","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Varizhuk","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.3390\/pharmaceutics14071453","article-title":"Precision anti-cancer medicines by oligonucleotide therapeutics in clinical research targeting undruggable proteins and non-coding RNAs","volume":"14","author":"Bartolucci","year":"2022","journal-title":"Pharmaceutics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1442","article-title":"Complex coacervate\u2010based materials for biomedicine","volume":"9","author":"Blocher","year":"2017","journal-title":"WIREs Nanomedicine Nanobiotechnology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1089\/nat.2020.0918","article-title":"Characterization of in vitro G-Quadruplex formation of imetelstat telomerase inhibitor","volume":"31","author":"Carloni","year":"2021","journal-title":"Nucleic Acid. 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