eric kmiec
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Re-engineering genomes using single stranded oligonucleotides and TAL-
effector Nucleases (TALENs) for industrial technology
Dr. Eric B. Kmiec
Center for Translational Cancer Research Helen F. Graham Cancer Center
Christiana Hospitaland
Delaware State University
Pure basic research(Bohr)
Use-inspired basic research(Pasteur)
Pure applied research(Edison)
“Pasteur’s Quadrant”
High
High
Low
Low
Quest for Fundamental
Understanding
Consideration of UseStokes, Donald. Pasteur's Quadrant Basic Science and Technology Innovation. Washington, DC: Brookings Institution Press, 1997. Print.
ssODN
ZFN
TALEN
Technologies and Tools
Gene Editing
CRISPR/Cas9
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Gene-Editing Model System
Regulation of Gene Editing
Oligonucleotide Enters Cell
Aligns in Homologous Register at Target Site
Creates D-loop
DNA Replication Activity
Transcriptional Activity
Homeologous Recombination
Activates DNA Damage Response Pathway
p53P
ATMP/ATRP
CHK1/CHK2P
Activation
Cell Cycle Delay (S)S phase stalling
H2AXP DS-BreakRepair
Coordinates Repair and Restart of Fork
Replication stallingFork Collapse
DS-Breaks
Incorporates into Target Site : replaces mutant
sequence
Gene conversion via Transcription-Coupled Repair
Gene conversion via Mismatch Repair
DNA Damage Elevates Gene
Editing Frequency
BLMHelicase
and/or
and/or
DNA Pairing Activity
RAD51(etc)
CellSurvival
The Kmiec Laboratory
2000-2011 Graduate StudentsHetal Parekh-Olmedo, Ph.D.Erin Brachman, Ph.D.Miya Drury, Ph.D.Luciana Ferrara, Ph.D.Katie McGuire, Ph.D.Julia Engstrom, Ph.D.Jennifer Sonntag, Ph.D.Kerry Falgowski, Ph.D.Jennifer Illuzzi, Ph.D.Melissa Bonner, Ph.D.Timothy Swartz, Ph.D.
Rohina NiamatBryan StrousePawel BialkNatalia RiveraShani SamuelBrett Sansbury
1995-2000 Graduate StudentsJoanne Sekiguchi, Ph.D.Allyson Cole-Strauss, Ph.D.Hideohito Kotani, Ph.D. Seema Dutta, Ph.D. Ronald Myers, Ph.D.
Postdoctoral FellowsDavid Gerhold,Ph.D.Kyggeon Yoon, Ph.D.
Postdoctoral FellowsSubhais Sandu, Ph.D.Dula Man, Ph.D
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