The Scharenberg Laboratory develops gene editing technologies and translational applications of these technologies in adoptive T-cell immunotherapies and hematopoietic stem cell gene therapy.
Led by Dr. Andrew Scharenberg, our lab has a particular interest developing new technologies to increase the efficiency and safety of gene editing. Our current research includes new approaches for nuclease expression in primary cell types, alternative approaches for provision of recombination templates, and methods for manipulation of the DNA repair machinery to promote recombination-based genome editing.
We collaborate with Dr. David Rawlings' laboratory on applications of homing endonucleases, TALENs and CRISPR nucleases for gene editing in hematopoietic stem cells, and for adoptive immunotherapies for autoimmune disease.
We also collaborate with Dr. Michael Jensen's laboratory on applications of gene editing for adoptive immunotherapy for oncology applications.
Andrew M. Scharenberg, MD, is an attending physician at Seattle Children's Hospital, and a professor in the Department of Pediatrics and adjunct professor in the Department of Immunology at the University of Washington School of Medicine. He participates in Seattle Children's Immunodeficiency Clinic and the Inpatient Immunology Consult Service, and is involved in teaching and graduate education at the University of Washington.
Scharenberg's clinical interests are focused on diagnosis and care of patients with inherited diseases of immune function, and the implementation of curative molecular therapies for these patients. His efforts in these activities are closely linked with the Scharenberg Laboratory's basic and translational work on gene editing technology.
Scharenberg received the American Pediatric Society/Society for Pediatric Research National Young Investigator Award in 2002, and is an active member of the American Society for Clinical Investigation and the American Pediatric Society. He was a co-founder of the gene-editing company Pregenen, acquired by bluebird bio in 2014.
In 2016, he was awarded a Pathways Visionary Award from the American Diabetes Association to support efforts to apply gene editing technology towards the development of stabilized regulatory T-cell therapeutics for therapy of type I diabetes.
Dr. Andrew Scharenberg has authored dozens of research papers, including the selected publications listed below. To see more of Scharenberg's publications, view a complete list on PubMed.
- megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering. Boissel S, Jarjour J, Astrakhan A, Adey A, Gouble A, Duchateau P, Shendure J, Stoddard BL, Certo MT, Baker D, Scharenberg AM. Nucleic Acids Res. 2013 Nov 26. [Epub ahead of print]
- Novel fluorescent genome editing reporters for monitoring DNA repair pathwayutilization at endonuclease induced breaks. Kuhar, R, Gwiazda1, K.S.,Humbert, O. Mandt, T.,, Pangallo, J.,, Brault, M., Khan, I., Maizels, N, Rawlings, D.J., Scharenberg AM, and Certo, M.T. Nucleic Acids Res. 2013 Oct 10. [Epub ahead of print]
- Coupling endonucleases with DNA end-processing enzymes to drive gene distribution. Certo M, Gwiazda K, Kuhar R, Sather B, Curinga G, Lambert A, Baxter S, Jacoby K, Brault M, Byoung R, Kiem HP, Gouble A, Paques F, Rawlings DJ, Scharenberg AM. 2012, Nat Methods. PMID2294164 [PubMed - as supplied by publisher]
- Engineering domain fusion chimeras from I-Onul family LAGLIDADG homingendonucleases. Baxter S, Lambert AR, Kuhar R, Jarjour J, Kulshina N, Parmeggiani F, Danaher P, Gano J, Baker D, Stoddard BL, Scharenberg AM. 2012, Nucleic Acid Res. PMID: 22684507 [PubMed - as supplied by publisher]
- Engineered Zinc Fingers Nickases Induce Homology-Directed Repair with ReducedMutagenic Effects. Ramirez CL, Certo MT, Mussolino C, Goodwin MJ, Cradick TJ, McCaffrey AP, Cathomen T, Scharenberg AM, Joung JK. 2012, Nucleic Acids Res. 40 (12):5560-5568. PMCID:PMC3384306
- Expanding LAGLIDADG Endonuclease Scaffold Diversity by Rapidly SuveyingEvolutionary Sequence Space. Jacoby K, Metzger M, Shen BW, Certo MT, Jarjour J, Stoddard BL, Scharenberg AM. 2012, Nucleic Acids Res. 40 (11):4957-64. PMCID:PMC3367166
- Tapping natural reservoirs of homing endonucleases for targeted gene modification. Takeuchi R, Lambert AR, Mak AN, Jacoby K, Dickson RJ, Gloor GB, Scharenberg AM, Edgell DR, Stoddard BL. Proc Natl Acad Sci U S A. 2011 Jul 22. PMCID:PMC3156218
- Tracking genome engineering outcome at individual DNA breakpoints. Certo MT, Ryu BY, Annis JE, Garibov M, Jarjour J, Rawlings DJ, Scharenberg AM. Nat Methods. 2011 Jul 10;8 (8):671-6. doi: 10.1038/nmeth.1648. PMCID:PMC3415300
- Competition Between PARP-1 and Ku70 Controls the Decision Between High-Fidelityand Mutagenic DNA Repair. Paddock, M., Bauman, A.T., Higdon, R., Kolker, E., Takeda, S., and Scharenberg AM. DNA repair, 2011 Mar 7, 10 (3):338-43. PMID:21256093
- The BRCT domain of PARP 1 is required for immunoglobulin gene conversion. Paddock, M, Buelow B, Takeda S, and Scharenberg AM. PLOS Biology, 2010 Jul 20;8 (7):e1000428. PMCID:PMC2907289
- High-resolution profiling of homing endonuclease binding and catalytic specificity usingyeast surface display. Jarjour J, West-Foyle H, Certo M, Hubert C, Getz M, Scharenberg AM. Nucleic Acids Res. 2009 Nov; 37 (20):68871-6870. PMCID:PMC27777416