2. F OLDING
Medical Utility
Now we know that the gene therapy
Gene therapy could be improved the health, because
this one intended make a cure for the
Molecular biology hereditary diseases by introducing
healthy genes; however the gene
therapy is also working in a way to
repair economical, effective and
Alejandra Baldiris Ardila biocompatible after disease, for
example like in the myocardium
Medical student
3 Semester Bibliography infarction, who is very important for
repair the heart and make it back to
normal working, which would have
great utility for people who suffered
Teacher heart disease.
• William E. Grose, K. Reed Clark, Danielle Also the gene therapy is making a
Lina Maria Martinez. S Griffin, Vinod Malik, Kimberly M. Shontz, new strategy for improve themselves,
Chrystal L. Montgomery, Sarah Lewis, Robert H.
Brown, Paul M. L. Janssen, Jerry R. Mendell, they are working in deliver large
Louise R. Rodino-Klapac. Homologous genes, doing this they could treating
Recombination Mediates Functional Recovery better some disease, because genes
of Dysferlin Deficiency following AAV5 Gene that were very large, are now
Transfer.PLoS ONE, 2012; 7 (6).
available to introduction.
• K. Zhu, H. Lai, C. Guo, D. Xu, C. Wang. Novel
vascular endothelial growth factor gene
delivery system-manipulated mesenchymal
stem cells repair infarcted
July 16- 2012 myocardium. Experimental Biology and
Medellin, Colombia Medicine, 2012.
3. F OLDING
AN ECONOMICAL, EFFECTIVE AND NEW GENE TRANSFER STRATEGY SHOWS PROMISE
BIOCOMPATIBLE GENE THERAPY STRATEGY FOR LIMB GIRDLE AND OTHER MUSCULAR
PROMOTES CARDIAC REPAIR DYSTROPHIES
This discovery, reported in the June 2012 issue of Experimental
Introduction Biology and Medicine, provides an economical, feasible and
biocompatible gene therapy strategy for cardiac repair. Science Daily (July 9, 2012) — The challenge of treating patients
Transplantation of VEGF gene manipulated mesenchymal stem cells with genetic disorders in which a single mutated gene is simply
The gene therapy is one (MSCs) has been proposed as a promising therapeutic method for too large to be replaced using traditional gene therapy techniques
technique in development who cardiac repair after myocardium infarction. However, the gene may soon be a thing of the past. A Nationwide Children's Hospital
delivery system, including the VEGF gene and delivery vehicle, needs study describes a new gene therapy approach capable of
use genetic to be optimized. On one hand, long-term and uncontrollable VEGF delivering full-length versions of large genes and improving
material in over-expression in vivo has been observed to lead to hemangioma skeletal muscle function. The strategy may hold new hope for
formation instead of functional vessels in animal models. On the
disease other hand, though non-viral gene vector can circumvent the
treating dysferlinopathies and other muscular dystrophies.
treatment, the limitations of virus, drawbacks of the current non-viral vectors, such
A group of untreatable muscle disorders known as
Principal objective as complex synthesis procedure, limited transfection efficiency and
dysferlinopathies are caused by mutations in the dysferlin gene.
high cytotoxicity, still needs to be overcome.
is introduction Co-investigators, Drs. Kai Zhu and Hao Lai, said "Hypoxia response Patients with these disorders, including limb girdle muscular
the healthy or elements were inserted into the promoter region of VEGF gene to dystrophy type 2B, are typically diagnosed in their early twenties.
form HRE-VEGF, which provided a safer alternative to the Approximately one-third will become wheelchair dependent by
missing genes.
conventionally available VEGF gene." "The HRE-VEGF up-regulates their mid-30s.
In one hand the gene expression under hypoxic conditions caused by ischemic Gene therapy using adeno-associated virus (AAV) to deliver
improve of gene myocardium and turns it off under normoxia condition when the genes to cells has been pursued as an option for some patients
regional oxygen supply is adequate." with muscular dystrophy. However, AAV's packaging limitations
therapy like the The hPAMAM nanoparticles, which exhibit high gene transfection have served as obstacles in using gene therapy to deliver large
new transfer efficiency and low cytotoxicity during the gene delivery process, can genes like dysferlin. Scientists in the past have attempted to work
strategy for large be synthesized by a simpler and more economical one-step/pot around AAV's packaging limitations by inserting a small version
polymerization technique. Drs. Zhu and Lai, said "Using the hPAMAM
genes, shows based gene delivery approach, our published and unpublished results
of large genes into the viral vector to induce gene expression.
Some have also used more than one viral vector at a time to
hope in favor of explicitly demonstrated that it was an economical, effective and
biocompatible gene delivery vehicle." deliver a large gene. However, micro and mini versions of large
muscular Dr Guo concluded that "Treatment with hPAMAM-HRE-VEGF genes don't always have the power of full-length gene expression
dystrophies, And in transfected MSCs after myocardium infarction improved the and an increased viral load can lead to negative side effects.
other hand new myocardial VEGF level, which improved graft MSC survival, increased
neovascularization and ultimately improved heart function. And this
economical, effective and novel VEGF gene delivery system may have clinical relevance for
biocompatible strategy for tissue repair in other ischemic diseases."
cardiac repair, will be available Dr. Steve Goodman, Editor-in-Chief of Experimental Biology and
Medicine said "Guo and colleagues have provided an exciting new
and use full to help and improve nanoparticle based gene therapy for cardiac repair. This novel I think that improve the gene therapy brings
the human life. approach has great promise for repair of the heart after myocardial
infarction." with it a lot of benefit ,also makes therapy be
more effective and safe for all the people who
In my opinion is very necessary investigation for improve the suffer any disease.
gene therapy, because in this case the entire patient who have,
a damaged tissue for ischemic diseases, will be incredibly
benefit.
4. I NTRODUCTION
The new transfer
strategy for large genes ,
shows hope in favor of
muscular dystrophies.
New economical,
effective and
biocompatible strategy
for cardiac repair.
5. N EW GENE TRANSFER STRATEGY SHOWS
PROMISE FOR LIMB GIRDLE AND OTHER
MUSCULAR DYSTROPHIES
SC IENC E D AILY ( J ULY 9 , 2 0 1 2 )
In the muscle disorders dysferlinopathies and
other muscular dystrophies , usually gene
therapy is using adeno- associate virus (AAV) to
deliver genes but, AAV’s have packaging
limitations to deliver large genes like dysferlin.
6. N EW GENE TRANSFER STRATEGY SHOWS
PROMISE FOR LIMB GIRDLE AND OTHER
MUSCULAR DYSTROPHIES
Using a small version of
large genes or more
than one viral vector at
the same time to deliver
is powerless and can
made negative side
effects.
7. N EW GENE TRANSFER STRATEGY SHOWS
PROMISE FOR LIMB GIRDLE AND OTHER
MUSCULAR DYSTROPHIES
A 2008 study revealed that in one serotype of
AAV (AAV5) could be package a large transcript
and at 2012 the Dr. Rodino- Klapac’s team used
the serotype to package a full-length, intact
dysferlin gene.
The gene was injected in leg muscles of dysferlin-
deficient mice.
8. N EW GENE TRANSFER STRATEGY SHOWS
PROMISE FOR LIMB GIRDLE AND OTHER
MUSCULAR DYSTROPHIES
They found that the
delivery of the large
gene was successful.
The most important was
the repaired membrane
deficits previously seen
in the dysferlin-deficient
mice, who give as a new
perception in the
therapy with large
genes.
9. O UTLOOK
I think that improve the
gene therapy brings with it
a lot of benefit ,also makes
therapy be more effective
and safe for all the people
who suffer any disease.
10. AN ECONOMICAL, EFFECTIVE AND
BIOCOMPATIBLE GENE THERAPY
STRATEGY PROMOTES CARDIAC REPAIR
S CIENCE D AILY (J ULY 6, 2012)
A new gene therapy, is
based in nanoparticle
hypoxia regulated vascular
endothelial (VEGF EDH)
growth factor, could be
replace the VEGF which is
more expensive and
uncontrollable.
11. AN ECONOMICAL, EFFECTIVE AND
BIOCOMPATIBLE GENE THERAPY
STRATEGY PROMOTES CARDIAC REPAIR
The transplantation of VEGF gene manipulated
mesenchymal stem cell is good because is not a
viral vector, so can evade the limitations of virus,
but have troubles with synthesis procedure,
limited transfection efficiency and high
cytotoxicity.
12. AN ECONOMICAL, EFFECTIVE AND
BIOCOMPATIBLE GENE THERAPY
STRATEGY PROMOTES CARDIAC REPAIR
They formed, with the promoter region of VEGF
hypoxia response elements: HRE-VEGF, who
regulate gene expression, under hypoxic
conditions and shut down in oxygen supply
adequate.
13. AN ECONOMICAL, EFFECTIVE AND
BIOCOMPATIBLE GENE THERAPY
STRATEGY PROMOTES CARDIAC REPAIR
The hPAMAM
nanoparticles are better in
a gene transfection
because is more efficacious
and have a low cytotoxicity.
Also treatment with
hPAMAM-HRE-VEGF
improved the myocardial
VEGF level, which increase
neovascularization and
improved heart function.
14. O UTLOOK
In my opinion is very
necessary investigation for
improve the gene therapy,
because in this case the entire
patient who have, a damaged
tissue for ischemic diseases,
will be incredibly benefit.
16. M EDICAL U TILITY
N EW G E N E T R A N S F E R S T R AT E GY S HO W S P RO M I S E FO R
LIMB GIRD L E AND O THER MUSC U L A R D Y STRO P H I E S
Can be useful in the future generation for get better
treating dysferlinopathies and other muscular
dystrophies.
17. M EDICAL U TILITY
AN ECONOMICAL, EFFECTIVE A N D B I O C O M PAT I B L E
GENE THERAPY S T R AT E G Y PROMOTES CARDIAC
R E PA I R
The new strategy brings grand hope for
repair of the heart after myocardial
infarction.
18. M EDICAL U TILITY
The gene therapy is available and use full to help
and improve the human life.
19. B IBLIOGRAPHY
William E. Grose, K. Reed Clark, Danielle Griffin, Vinod Malik,
Kimberly M. Shontz, Chrystal L. Montgomery, Sarah Lewis, Robert
H. Brown, Paul M. L. Janssen, Jerry R. Mendell, Louise R. Rodino-
Klapac. Homologous Recombination Mediates Functional Recovery
of Dysferlin Deficiency following AAV5 Gene Transfer.PLoS ONE,
2012; 7 (6)
K. Zhu, H. Lai, C. Guo, D. Xu, C. Wang. Novel vascular endothelial
growth factor gene delivery system-manipulated mesenchymal
stem cells repair infarcted myocardium. Experimental Biology and
Medicine, 2012
