Gene therapy refers to the transfer of genetic information with the intend to cure a diases. In our lab, we focus on gene therapy for a variety of immune disorders. Our main emphasis is on treatment of severe combined immune deficiency (SCID), sometimes called bubble boy disease, and other primary immune deficiencies such as XLA (BTK-disease). Cossu, Italian Journal of Pediatrics 2010. Currently we are close to clinical implementation of gene therapy for RAG1-deficient SCID. Soon you can find updates here with information for patients and their parents. We closely collaborate with the Willem Alexander Children Clinic at LUMC and the patient advocacy group Stichting afweer stoornissen.
Techniques and methods used include:
- Genetic or conditional knockout mouse models (Rag1, Rag2, Btk)
- Models for transplantation of human stem cells (NSG)
- Retro- or lentiviral expression of transgenes
- Cell sorting by FACS
- mRNA expression measurements (qPCR, microarray, RNASeq)
- 12-color flow cytometry
- Lentiviral transduction
- TCR and BCR repertoire assessment
Relevant publications:
Anna-Sophia Wiekmeijer, Karin Pike-Overzet, Martijn H Brugman, Ingrid LM Wolvers-Tettero, Arjan C Lankester, Robbert GM Bredius, Jacques JM van Dongen, Willem E Fibbe, Anton W Langerak, Mirjam van der Burg, Frank JT Staal
J Allergy Clin Immunol. 2015, accepted for publication.
PMID: 26441229
Pike-Overzet K, Baum C, Bredius RG, Cavazzana M, Driessen GJ, Fibbe WE, Gaspar HB, Hoeben RC, Lagresle-Peyrou C, Lankester A, Meij P, Schambach A, Thrasher A, Van Dongen JJ, Zwaginga JJ, Staal FJ.
J Allergy Clin Immunol. 2014 Jul;134(1):242-3. doi: 10.1016/j.jaci.2014.04.033. Epub 2014 Jun 26.
PMID: 25117803
Wiekmeijer AS, Pike-Overzet K, Brugman MH, Salvatori DC, Egeler RM, Bredius RG, Fibbe WE, Staal FJ.
Biores Open Access. 2014 Jun 1;3(3):110-6. doi: 10.1089/biores.2014.0008.
PMID: 24940562
Mikkers H, Pike-Overzet K, Staal FJ.
Pediatr Res. 2012 Apr;71(4-2):427-432. doi: 10.1038/pr.2011.65. Epub 2012 Feb 8.
PMID: 22430378
Hendriks RW, Bredius RG, Pike-Overzet K, Staal FJ.
Expert Opin Ther Targets. 2011 Aug;15(8):1003-21. doi: 10.1517/14728222.2011.585971. Epub 2011 Jun 2.
PMID: 21635151
Pike-Overzet K, Rodijk M, Ng YY, Baert MR, Lagresle-Peyrou C, Schambach A, Zhang F, Hoeben RC, Hacein-Bey-Abina S, Lankester AC, Bredius RG, Driessen GJ, Thrasher AJ, Baum C, Cavazzana-Calvo M, van Dongen JJ, Staal FJ.
Leukemia. 2011 Sep;25(9):1471-83. doi: 10.1038/leu.2011.106. Epub 2011 May 27.
PMID: PMID: 21617701
Ng YY, Baert MR, Pike-Overzet K, Rodijk M, Brugman MH, Schambach A, Baum C, Hendriks RW, van Dongen JJ, Staal FJ.
Leukemia. 2010 Sep;24(9):1617-30. Epub 2010 Jun 24.
PMID: 20574453