Gene therapy involves inserting functioning genes into patients' cells to treat genetic diseases. It has been studied as a potential treatment for cancers, blood diseases, immune and neurological disorders. There are two main types - somatic cell gene therapy targets specific cells/tissues, while germline gene therapy affects heritable genetic material. Recent progress includes the first approved gene therapy in 1990 and advancements in viral vectors. Major milestones in the 2000s-2010s included treatments for leukemia, ADA-SCID, and retinal diseases. Future prospects are promising with CRISPR/Cas9 offering more precise gene editing and many ongoing clinical trials, though challenges remain around costs, technical expertise, and ethical concerns.

1. Gene Therapy
Current progress and Future prospects

2. Gene Therapy
Gene therapy
• Is the insertion of genes into an individual’s cells and tissue
to treat a disease
• Has been studied as a potential treatment for genetic
disease.
• A vector must be used to deliver the therapeutic gene to the
target cell.
• A functioning copy of the gene is packaged into a vector.
• Modified virus acts as a transport vehicle for functioning
gene.

3. Gene Therapy
Study purpose of gene therapy
This is treatment for many disease.
For example,
• Cancers
• Blood disease
• Central nervous system disease
• Immune system disease
• Cardiovascular disease
• Muscular dystrophy
• Huntington’disease

4. Gene Therapy
Types
There are two types of gene therapy.
1. Somatic cell gene therapy
2. Germ line gene therapy

5. Gene Therapy

6. Gene Therapy

7. History

8. Gene Therapy

9. Gene Therapy
Progression 90s
• The first approved gene therapy
clinical research in the US took
place on 14 September 1990.
• Four-year-old Ashanti DeSilva
received treatment for a genetic
defect.
• The effects were successful, but
temporary.
Fig: Ashanti DeSilva

10. Gene Therapy
Progression 90s
• Cancer gene therapy was introduced in 1992/93.
• The beginning of cancer immunogene therapy.
• Effective due to the anti-tumor mechanism of IGF-I
antisense.

11. Gene Therapy
Progression 2000s
 The modified cancer gene therapy strategy of antisense IGF-I
RNA
 Has shown promising results in the treatment of six different
malignant tumors.
They are,
 Glioblastoma,
 Cancers of liver,
 Colon,
 Prostate,
 Uterus,
 Ovary,

12. Gene Therapy
Progression 2000s
 Repaired errors in messenger RNA derived
from defective genes has the potential to
treat thalassaemia, cystic fibrosis and some
cancers. (2002)
 Gendicine delivers the tumor suppressor
gene p53 using an engineered adenovirus
for the treatment of head and neck
squamous cell carcinoma. Fig: Head and neck
cancer

13. Gene Therapy
Progression 2000s
 Successfully treated metastatic melanoma in two patients
using killer T cells genetically retargeted to attack the cancer
cells. (2006)
 Successful use of gene therapy to treat two adult patients for
X-linked chronic granulomatous disease, a disease which
affects myeloid cells and damages the immune system.
(2006)

14. Gene Therapy
Progression 2000s
 Use of VRX496, a gene-based immunotherapy for
the treatment of HIV that uses a lentiviral vector to
deliver an antisense gene against the HIV
envelope(2006)
 Researchers announced the first gene therapy trial
for inherited retinal disease. (2007)

15. Gene Therapy
Progression 2010s
 An 18-year-old male patient in France with beta-thalassemia
had been successfully treated in 2010.
 Human HGF plasmid DNA therapy of cardiomyocytes is a
potential treatment for coronary artery disease and
myocardial infarction. (2011)
 The FDA approved Phase 1 clinical trials on thalassemia
major patients in the US for 10 participants in 2012.

16. Gene Therapy
Progression 2010s
 10 of 13 patients with multiple myeloma were in remission or
very close to it three months after being injected with a
treatment involving genetically engineered T cells (2012).
 Three of five adult subjects who had acute lymphocytic
leukemia (ALL) had been in remission for five months to two
years after being treated with genetically modified T cells
(2013)

17. Gene Therapy
Progression (2010s)
 Two children born with adenosine
deaminase severe combined
immunodeficiency disease (ADA-
SCID) had been treated with
genetically engineered stem cells
18 months previously and that
their immune systems were
showing signs of full recovery.
(2013)
Fig: Alysia Padilla-Vacarro and daughter
Evangelina on the day of her gene
therapy treatment

18. Gene Therapy
Progression (2010s)
 Six choroideremia patients had
been treated with adeno-
associated virus with a copy of
REP1. (2014)
 Clinical trials of gene therapy for
sickle cell disease were started in
2014.

19. Gene Therapy
Progression (2010s)
 A baby girl Layla Richards treated with
an experimental treatment using donor
T-cells genetically engineered using
TALEN to attack cancer cells. (2015)
 A trial to genetically modify T-cells
from 10 adult patients with lung cancer
and reinject the modified T-cells back
into their bodies to attack the cancer
cells. (2016)
Fig: Layla Richards

20. Gene Therapy
Progression (2010s)
 The FDA approved tisagenlecleucel for acute
lymphoblastic leukemia. (2017)
 This is the first form of gene therapy to be
approved in the United States.
 Six of the seven patients on the high dose regime
increased the level of the blood clotting VIII to
normal levels. (2017)

21. Gene Therapy
Progression (2010s)
 The FDA approved Luxturna, the first in vivo gene therapy,
for the treatment of blindness due to Leber's congenital
amaurosis.
 Spark Therapeutics has been rewarded with an FDA approval
for their Luxturna therapy. (2018)
 Clinical trials by Sangamo involving gene editing using Zinc
Finger Nuclease (ZFN) are ongoing. (2019)

22. Future of Gene Therapy
 The FDA approved the first gene therapy in 2017,
marking a significant moment in the history of health
care.
 CRISPR/Cas9 gene-editing technology offer better and
more effective gene therapies for various conditions
 It is now being evaluated as a treatment for multiple
cancers, HIV, and other potentially life-threatening
conditions.
 The number of companies pursuing gene therapies has
rapidly increased.

23. Future of Gene Therapy
Gene therapies in development
1. ADA-SCID
2. Alpha-1 antitrypsin (A1AT) deficiency
3. β-thalassemia (severe sickle cell)
4. Cerebral adrenoleukodystrophy (CALD)
5. Choroideremia
6. Cystic Fibrosis
7. Glaucoma
8. Wiskott Aldrich syndrome (WAS)
9. Hemophilia A
10. Hemophilia B
11. IRD (vision loss)
12. Metachromatic leukodystrophy
13. MPS I (Hurler syndrome)
14. MPS II (Hunter’s syndrome)
15. Pompe Disease
16. Spinal Muscular Atrophy (SMA)
17. X-linked myotubular myopathy

24. Future of Gene Therapy
Human clinical trials based on gene editing technology
(updated 2019)
1. Cancer (PD-1 knockout)
2. Hemoglobinopathies (β-thalassemia, sickle cell disease)
3. Hemophilia B
4. HIV
5. MPS I (Hurler syndrome)
6. MPS II (Hunter’s syndrome)
All of the trials above involve somatic cell gene editing in humans.

25. Limitation of Gene Therapy
 Lack of knowledge about the disease at the
DNA level
 Multiple gene effects cannot be treated
today
 Affected tissue must be accessible to gene
therapy
 In case of dominant disorder, homologous
rearrangement has to occur for successful
replacement of defective gene.

26. Limitation of Gene Therapy
 Retroviral contamination and spread in
the body.
 High technical expertise required.
 Many ethical questions to be answer
properly.
 Gene therapies priced between 1 and 3
million dollars.
 Spark is selling Luxturna for 425K per
eye, so 850K for both eyes.

27. Thank
You