PT  - JOURNAL ARTICLE
AU  - Munevver Cinar
AU  - Lourdes Martinez-Medina
AU  - Pavan K. Puvvula
AU  - Arsen Arakelyan
AU  - Badri N. Vardarajan
AU  - Neil Anthony
AU  - Ganji P. Nagaraju
AU  - Dongkyoo Park
AU  - Lei Feng
AU  - Faith Sheff
AU  - Marina Mosunjac
AU  - Debra Saxe
AU  - Steven Flygare
AU  - Olatunji B. Alese
AU  - Jonathan Kaufman
AU  - Sagar Lonial
AU  - Juan Sarmiento
AU  - Izidore S. Lossos
AU  - Paula M. Vertino
AU  - Jose A. Lopez
AU  - Bassel El-Rayes
AU  - Leon Bernal-Mizrachi
TI  - Retrotransposons facilitates tissue specific horizontal transfer of circulating tumor DNA between human cells
AID  - 10.1101/2022.08.10.501131
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.10.501131
4099  - http://biorxiv.org/content/early/2022/08/11/2022.08.10.501131.short
4100  - http://biorxiv.org/content/early/2022/08/11/2022.08.10.501131.full
AB  - A variety of organisms have been shown to have altered physiology or developed pathology due to gene transfer, but mammals have never been shown to do so. Here, we show that circulating tumor DNA (ct) can promote cell-specific horizontal gene transfer (HGT) between human cancer cells and explain the mechanisms behind this phenomenon. Once ctDNA enters the host cell, it migrates to the nucleus and integrates into the cell’s genome, thereby transferring its genetic information. We determine that retrotransposons of the ERVL, SINE, and LINE families are necessary for cell targeting and the integration of ctDNA into host DNA. Using chemically synthesized retrotransposons, we found that AluSp and MER11C reproduced multiple myeloma’s (MM) ctDNA’s cell targeting and integration into MM cells. We also discovered that ctDNA might, as a result of HGT, influence the treatment response of multiple myeloma and pancreatic cancer models. Overall, this is the first study to show that retrotransposon-directed HGT can promote genetic material transfer in cancer. There is, however, a broader impact of our findings than just cancer since cell-free DNA has also been found in physiological and other pathological conditions as well. Furthermore, with the discovery of transposons-mediated tissue-specific targeting, a new avenue for the delivery of genes and therapies will emerge.Competing Interest StatementLourdes Martinez-Medina, Pavan K. Puvvula and Lei Feng are employee by Kodikaz therapeutic solutions. Owner of the patent for the use of transposons described in this manuscript. Leon Bernal-Mizrachi is founder and consultant for Kodikaz Therapeutic Solutions, LLC