![]() ![]() Genetic applications of an inverse polymerase chain reaction. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack MP, Wulffraat N, Leboulch P et al. Acute myeloid leukemia is associated with retroviral gene transfer to hematopoietic progenitor cells in a rhesus macaque. Seggewiss R, Pittaluga S, Adler RL, Guenaga FJ, Ferguson C, Pilz IH et al. Murine leukemia induced by retroviral gene marking. Li Z, Dullmann J, Schiedlmeier B, Schmidt M, von Kalle C, Meyer J et al. Murine leukemia virus vector integration favors promoter regions and regional hot spots in a human T-cell line. Tsukahara T, Agawa H, Matsumoto S, Matsuda M, Ueno S, Yamashita Y et al. Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells. ![]() Recchia A, Bonini C, Magnani Z, Urbinati F, Sartori D, Muraro S et al. The use of retroviral vectors for gene therapy-what are the risks? A review of retroviral pathogenesis and its relevance to retroviral vector-mediated gene delivery. Cold Spring Harbor Laboratory Press: New York, 1997, pp 161–203.Īnson DS. In: Coffin JM, Hughes SH, Varmus HE (eds). Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped gammaretroviral vector. Gaspar HB, Parsley KL, Howe S, King D, Gilmour KC, Sinclair J et al. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, De Villartay JP et al. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. It provides a basis for large-scale insertion site analyses, which is now urgently needed to discover novel gene therapy vectors with ‘safe’ insertion profiles.Īiuti A, Slavin S, Aker M, Ficara F, Deola S, Mortellaro A et al. ![]() Thus, for the first time a tool allowing high-throughput profiling of gene therapy vector insertion sites is available. Additionally, all experimental frequencies are compared with the data obtained from a reference set, containing 1 000 000 random integrations (‘random set’). We developed a tool termed QuickMap, which uniformly maps and analyzes human and murine vector-flanking sequences within seconds (available at Besides information about hits in chromosomes and fragile sites, QuickMap automatically determines insertion frequencies in +/− 250 kb adjacency to genes, cancer genes, pseudogenes, transcription factor and (post-transcriptional) miRNA binding sites, CpG islands and repetitive elements (short interspersed nuclear elements (SINE), long interspersed nuclear elements (LINE), Type II elements and LTR elements). Although remarkable progress has been achieved in mapping gene therapy vector insertion sites, public reference sets are lacking, as are the possibilities to quickly detect non-random patterns in experimental data. For the construction of such profiles, vector-flanking sequences detected by inverse PCR, linear amplification-mediated-PCR or ligation-mediated-PCR need to be mapped to the host cell's genome and compared to a reference set. Several events of insertional mutagenesis in pre-clinical and clinical gene therapy studies have created intense interest in assessing the genomic insertion profiles of gene therapy vectors. ![]()
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