666 Lentiviral Vectors Tailored for Liver Directed Gene Therapy Do Not Show Any Detectable Genotoxicity in Sensitive In Vivo Biosafety Assays Molecular Therapy Volume 21, Supplement 1, May 2013 Copyri[.]
HEMATOLOGIC AND IMMUNOLOGIC GENE & CELL THERAPY II 250 bp cHS4 core used in a -thalassemia gene therapy trial revealed cryptic splice sites in the cHS4-core, resulting in aberrant splicing of the HMGA2 gene and deletion of one core upon integration The sGbG350 LV contains the 250 bp core; hence we generated custom insulators using a combination of FP 1-7 in varied frequency and orientation (termed MFO 0-5) but devoid of the cryptic splice site Southern blot shows stable proviral transmission of all LV carrying these insulators in transduced murine erythroleukemic (MEL) cells In a plasmid-based assay we found that MFO-1, MFO-2 and MFO-4 insulators possess significantly strong EBA compared to an uninsulated plasmid (P