Mutagenesis by retroviral transgene insertion: risk assessment and potential alternatives.
Focus on retroviral gene transfer into hematopoietic cells has previously led to a proposed classification of side effects and discussion of issues related to combinatorial toxicity (including oncogenicity) of genetic interventions. Recent data underline that this discussion has to be broadened to any type of stable transfer technology. This review summarizes insights obtained in cell culture and animal models that were specifically designed to evaluate side effects of transgene insertion and new approaches of insertion site targeting. Ongoing research aims to reduce side effects of therapeutic transgene insertion by dose optimization and definition of contributing risk factors.
Baum
Christopher
C
Department of Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. baum.christopher@mh-hannover.de
Fehse
Boris
B
D001483:Base Sequence; D018628:Gene Dosage; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D009369:Neoplasms / Q000503:physiopathology; D011995:Recombination, Genetic; D012190:Retroviridae / Q000235:genetics* / Q000378:metabolism; D018570:Risk Assessment; D019076:Transgenes