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We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE\u00a0or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicated multiple myeloma (MM) ctDNA cell targeting and integration. Additionally, we found that ctDNA may alter the treatment response of MM and pancreatic cancer models. This study shows that retrotransposon DNA sequences promote cancer gene transfer. However, because cell-free DNA has been detected in physiological and other pathological conditions, our findings have a broader impact than just cancer. Furthermore, the discovery that transposon DNA sequences mediate tissue-specific targeting will open up a new avenue for the delivery of genes and therapies.<\/jats:p>","DOI":"10.1093\/nar\/gkae427","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T03:26:11Z","timestamp":1716521171000},"page":"7539-7555","source":"Crossref","is-referenced-by-count":5,"title":["Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells"],"prefix":"10.1093","volume":"52","author":[{"given":"Munevver","family":"Cinar","sequence":"first","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University , Atlanta, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Martinez-Medina","sequence":"additional","affiliation":[{"name":"Kodikaz Therapeutic Solutions, Inc , New\u00a0York , NY, 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