en علوم پزشکی Medical Sciences مقاله مروری Review Article In this paper, we analyze how the idea of universal donors has developed from the classic serological ABO system through to the novel approaches in genomic bioengineering. First, we discuss the existing paradigm of type O blood being used as universal donors and the drawbacks associated with the use of serological matching, particularly in the context of organ transplantation. Then, using a literature review on the latest advancements, we describe new approaches for making universal donors, such as blood group antigen enzymatic conversion and CRISPR-Cas9 gene editing, which make it possible to produce hypoimmunogenic cells. Main barriers to developing these technologies lie in the balance between T lymphocytes and natural killer (NK) cell immune response, genetic diversity within a population, and implementation of novel bioengineering approaches in a clinical setting. Universal Donor, Genomic Bioengineering, Serologic Compatibility, Transplantation. 32 40 http://modernmedlab.com/browse.php?a_code=A-10-73-21&slc_lang=en&sid=1 Elisa Rahmati elissarahmati7@gmail.com 10031947532846002315 10031947532846002315 No Students' Scientific Research Center (SSRC), Tehran university of medical sciences, Tehran, Iran Shayan Farzanbakhsh shayan.farzanb@yahoo.com 10031947532846002316 10031947532846002316 No Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. Massoud Vosough masvos@yahoo.com 10031947532846002317 10031947532846002317 Yes Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.