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However, no ASO\u2010based anticancer drugs are currently available, largely because of limited therapeutic efficacy. Conventional ASO\u2010based cancer therapies typically target oncogenes or cancer\u2010associated genes because constitutively active ASOs may also damage normal tissues. We hypothesized that this limitation can be overcome by conditionally activating ASOs only in response to cancer\u2010specific biomarkers. In this paradigm, therapeutic efficacy is determined by the potential of the released ASO rather than by the cancer specificity of its target, allowing any gene essential for cell survival to serve as a target. Our aim was to identify the most cytotoxic ASO sequences for cancer cells. We designed 37 ASOs targeting 13 candidate genes and evaluated them in human ovarian adenocarcinoma (SKOV3) and lung adenocarcinoma (A549) cell lines. An ASO targeting\n                    <jats:italic>DARS1<\/jats:italic>\n                    exhibited the strongest activity, inducing apoptotic cell death in both cell types. Additional ASOs targeting\n                    <jats:italic>DYNC1I2<\/jats:italic>\n                    and\n                    <jats:italic>EIF2S3<\/jats:italic>\n                    were identified as effective candidates in SKOV3 and A549 cells, respectively. Importantly, the selected ASOs exhibited low toxicity toward the tested noncancerous cell line. These findings identify\n                    <jats:italic>DARS1<\/jats:italic>\n                    ,\n                    <jats:italic>DYNC1I2<\/jats:italic>\n                    , and\n                    <jats:italic>EIF2S3<\/jats:italic>\n                    as promising targets for marker\u2010dependent ASO\u2010based cancer therapy.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70544","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:32:36Z","timestamp":1790537556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Highly Cytotoxic Antisense Oligonucleotides Targeting Essential Genes in Human Ovarian and Lung Cancer Cells"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9763-5209","authenticated-orcid":false,"given":"Zain","family":"Hussein","sequence":"first","affiliation":[{"name":"Center for Molecular and Biological Technologies ITMO University  St. Petersburg Russian Federation"},{"name":"Laboratory of Nucleic Acid Nanotechnology ITMO University  St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3322-8080","authenticated-orcid":false,"given":"Elena V.","family":"Misnik","sequence":"additional","affiliation":[{"name":"Laboratory of Nucleic Acid Nanotechnology ITMO University  St. Petersburg Russian Federation"},{"name":"Institute of Gene Biology Russian Academy of Sciences  Moscow Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera","family":"Alaji","sequence":"additional","affiliation":[{"name":"Center for Molecular and Biological Technologies ITMO University  St. Petersburg Russian Federation"},{"name":"Laboratory of Nucleic Acid Nanotechnology ITMO University  St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4658-5281","authenticated-orcid":false,"given":"Christina","family":"Patra","sequence":"additional","affiliation":[{"name":"Center for Molecular and Biological Technologies ITMO University  St. Petersburg Russian Federation"},{"name":"Laboratory of Nucleic Acid Nanotechnology ITMO University  St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6264-6760","authenticated-orcid":false,"given":"Rami","family":"Mhanna","sequence":"additional","affiliation":[{"name":"Center for Molecular and Biological Technologies ITMO University  St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0862-1159","authenticated-orcid":false,"given":"Abadeer","family":"Habib","sequence":"additional","affiliation":[{"name":"Laboratory of Nucleic Acid Nanotechnology ITMO University  St. Petersburg Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Eldeeb","sequence":"additional","affiliation":[{"name":"Laboratory of Nucleic Acid Nanotechnology ITMO University  St. Petersburg Russian Federation"},{"name":"Belozersky Institute of Physico\u2010Chemical Biology Lomonosov Moscow State University  Moscow Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8682-6553","authenticated-orcid":false,"given":"Dmitry M.","family":"Kolpashchikov","sequence":"additional","affiliation":[{"name":"Chemistry Department University of Central Florida  Orlando Florida USA"},{"name":"Burnett School of Biomedical Sciences University of Central Florida  Orlando Florida USA"},{"name":"National Center for Forensic Science University of Central Florida  Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"StatPearls [Internet]","author":"Moleyar\u2010Narayana P.","year":"2024"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.15537\/1658-3175.8333"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201016\u20101536"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00261"},{"key":"e_1_2_10_6_1","volume-title":"StatPearls","author":"Amjad M. 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