Biology Reference
In-Depth Information
FIGURE 1.8
Types of inhibitors that fight tumori-
genic activities. Original artwork provided by Scott Lee
Visual Design.
FIGURE 2.2
Mechanism of MGMT repair. In this figure, an
example of methylating agents, TMZ, is used to induce a methyl
adduct on DNA. MGMT recognizes the adduct, and binds to the
DNA. Amino acid with the adduct is then flipped out, and the methyl
group is transferred to a cysteine residue on MGMT active site. The
transfer is permanent, and MGMT protein is then destined for
degradation. DNA is repaired.
Cysteine residue (145)
G C O
6
-Methylguanine
A T
Temozolomide
Degradation
CH
3
MGMT
CH
3
MGMT
CH
3
MGMT
MGMT mediated repair
Repaired DNA
HSCs
MGMT-P140K
transfer vector
Gene-modified HSCs
Endogenous HSC
MGMT-P140K HSC
FIGURE 2.3
MGMT-P140K gene therapy. Human HSCs are mobilized in peripheral blood and collected. MGMT-P140K gamma-retroviral or
lentiviral vector will deliver MGMT-P140K gene into HSCs ex vivo. Then transduced heterogeneous population of HSCs will be infused back into
the patient. After HSCs home to their hematopoietic niches, MGMT-P140K is expressed in active HSCs.
