title: The flawed scientific basis of the altered nuclear transfer-oocyte assisted reprogramming (ANT-OAR) proposal.
abstract: First put forth in June 2005, the altered nuclear transfer-oocyte assisted reprogramming (ANT-OAR) proposal has been promoted as an ethically-acceptable alternative to the embryo-destructive methods now used to obtain embryonic stem cells. According to its proponents, the goal of ANT-OAR is to use the cloning process to create a pluripotent stem cell. This would be achieved through overexpression of the transcription factor Nanog (or a hypothetical substitute) both in the enucleated egg cell and in the somatic cell prior to transfer of its nucleus. Although the ethical acceptability of ANT-OAR has been publicly debated, its scientific feasibility has not. This paper aims to help rectify this situation. It argues that ANT-OAR, as currently conceived, cannot realistically work. It presents evidence from the scientific literature showing that Nanog cannot single-handedly establish pluripotency in cells, but rather works together with a network of other transcription factors to maintain pluripotency. It argues that ANT-OAR is based on a flawed understanding of stem cell biology, and emphasizes that, in this debate about embryonic stem cells, scientists must strive to accurately and realistically assess the feasibility of the embryo research strategies they propose.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Howard University, 520 W Street, NW, Washington, DC 20059, USA. wbyrnes@howard.edu
authors.forename: W Malcolm
authors.initials: WM
authors.lastname: Byrnes
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D065150:Cellular Reprogramming / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D033041:Embryo Research / Q000941:ethics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D051188:Knowledge Bases; D000071317:Nanog Homeobox Protein; D053652:Nuclear Transfer Techniques; D009865:Oocytes / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology; D012107:Research Design
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein