title: Gene Insertion Into Genomic Safe Harbors for Human Gene Therapy.
abstract: Genomic safe harbors (GSHs) are sites in the genome able to accommodate the integration of new genetic material in a manner that ensures that the newly inserted genetic elements: (i) function predictably and (ii) do not cause alterations of the host genome posing a risk to the host cell or organism. GSHs are thus ideal sites for transgene insertion whose use can empower functional genetics studies in basic research and therapeutic applications in human gene therapy. Currently, no fully validated GSHs exist in the human genome. Here, we review our formerly proposed GSH criteria and discuss additional considerations on extending these criteria, on strategies for the identification and validation of GSHs, as well as future prospects on GSH targeting for therapeutic applications. In view of recent advances in genome biology, gene targeting technologies, and regenerative medicine, gene insertion into GSHs can potentially catalyze nearly all applications in human gene therapy.
authors: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|The Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Eirini P
authors: EP
authors: Papapetrou
authors: Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany.|Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Axel
authors: A
authors: Schambach
mesh_terms: D015316:Genetic Therapy / Q000379:methods*; D015894:Genome, Human; D006801:Humans; D016254:Mutagenesis, Insertional / Q000379:methods*; D019076:Transgenes