4. What is Gene Therapy?What is Gene Therapy?
Gene therapy is a technique for
introducing the genetic material of a gene
in a patient that lacks that gene because
of a mutation.
5. VectorsVectors
The way you insert the “normal” gene in
the patient’s cell is by vectors.
The most common vectors that are used
in gene therapy are virus vectors
6. Why Viruses?Why Viruses?
Viruses through the time of evolution
have evolved to infect the cells with great
specificity
Viruses tend to be very efficient at
transfecting their own DNA into the host
cell genome.
This allows them to produce new viral
particles at the period of synthesis of the
cell
7. Types Of Viruses…Types Of Viruses…
Retrovirus
Adinovirus
Lentiviruses
Poxviruses
and Herpes Viruses
8. Adenovirus
36 kb Double Stranded DNA Genome
Entry through CAR receptor and integrin co-receptor
10. Which Virus to Use?Which Virus to Use?
Depends
how well they transfer the genes to cells
which cells they can recognize and infect
and whether they alter the cell’s DNA permanently
or temporarily
11. Cells removed from body
Transgene delivered
Cells cultured
Cells returned to the body
Ex Vivo In Vivo
Transgene delivered
directly into host
Strategies for Transgene Delivery
12. Which cells are the target cellsWhich cells are the target cells
Both Healthy and Cancerous cells can be
a target
Ex of targeting Healthy cells
◦ One way is by replacing a missing or altered
gene with a “normal” one
13. Cont: Which cells are theCont: Which cells are the
target cellstarget cells
Ex of targeting Cancer Cells
Scientists can target cancer cells with genes that
can be used to destroy the cells. In this
technique, cancer cells are introduced to what is
called “suicide genes”
18. Using Gene Therapy toUsing Gene Therapy to
Treat Lung CancerTreat Lung Cancer
In this clinical trial the scientist used gene
therapy in combination with radiation
therapy so they can treat lung cancer in
19 different patients
19. Treatment: Gene therapyTreatment: Gene therapy
and Radiation.and Radiation.
Intratumoral needle injections of Ad-p53
on days 1, 18 and 32 of the treatment.
tumors ≥ 4 cm where injected with 10 ml
tumors ‹ 4 cm were injected with 3 ml
Radiation therapy
20. ResultsResults
17/19 patients made it through the entire
therapy
complete response in 2 patients (11%)
partial response in 4 patients (21%)
stable disease in 1 patient (5%)
progressive disease in 11 patients (57%)
21.
22. Results Not That GoodResults Not That Good
57% of the patients showed that the
cancer progressed to worse stages
Why?
23. Major Problems thatMajor Problems that
Scientists Must OvercomeScientists Must Overcome
Identify more efficient ways to deliver the
genes to the patients’ genetic material
Develop vectors that can specifically focus
on the targeted cells
Ensure that vectors will successfully insert
the desired genes into each of these
target cells
24. Cont: Major Problems thatCont: Major Problems that
Scientists Must OvercomeScientists Must Overcome
Deliver genes to a precise location in the
patient’s DNA
Ensure that transplanted genes are
precisely controlled by the body’s normal
physiologic signals
Editor's Notes
A, patient no. 2: left upper lobe tumor unable to undergo surgery because of poor pulmonary function and cardiac disease. Patient received three injections of Ad-p53 (3 _ 1011 vp) via bronchoscope in combination with radiation therapy (60 Gy; A). Pathologic biopsy negative for viable tumor 3 months after completion of therapy (B). B, patient no. 3: right upper lobe tumor unable to be treated with surgery because of poor pulmonary function and ineligible for chemotherapy because of cardiac disease and obstructed bronchus (5/29/98). Patient was treated with three injections of Ad-p53 (3 _ 1011 vp) and radiation therapy (60 Gy) by bronchoscopy (5/29/98) with a CR 3 months after completion of therapy (10/8/98) and no pathologic evidence of tumor 29 months after therapy (12/11/00).
