GENE THERAPY

The history part of it!

What is gene therapy?

Gene therapy is the use of DNA as a pharmaceutical

agent to treat disease.

The most common form of gene therapy involves using

DNA that encodes a functional, therapeutic gene to replace a mutated gene.

General mechanism
In gene therapy, DNA that encodes a therapeutic protein

is packaged within a vector", which is used to get the DNA inside cells within the body.
Once inside, the DNA becomes expressed by the cell

machinery, resulting in the production of therapeutic protein, which in turn treats the patient's disease.

Types of gene therapy

Somatic gene therapy

Germ line gene therapy

History

1989
S.A. Rosenberg aimed at using gene marking techniques

to:
- track the movements of tumour-infiltrating blood cells in cancer patients .

What did he do?

- He extracted the TILs from metastatic melanoma patients
- performed retroviral gene transfer to introduce a marker

gene to these cells after

- re-administered them back to the patients.

Therapeutic trial:

He treated two patients with

ex vivo modified TILs expressing tumour necrosis factor.

Results of the trial

- revealed that the tumours did not grow at the injection site

- here was no evidence of viable tumour cells when these

sites were surgically resected approximately 3 weeks after injection

1990
In 1990, Martin Cline attempted gene therapy using

recombinant DNA.
He applied to the UCLA Human Subjects committee for

permission to carry out the same approach for treating patients suffering from -thalassemia.
Cline initiated the study and extracted bone marrow cells

from two -thalassemia patients.

September 14th 1990

FDA approved the first time a gene therapy trial with a

therapeutic attempt in humans.

Two children suffering from adenosine deaminase

deficiency (ADA-SCID) were treated

1999
Jesse Gelsinger

Died at the age of 18

2003
In 2003, China became the first country to approve a

gene therapy based product for clinical use.

Gendicine is an adenoviral vector used to treat patients

with head and neck squamous cell carcinoma cancer

The E1 region is replaced by p53

Mechanism:

2005
Two years after approving Gendicine, the Chinese SFDA

granted approval of another gene therapy product, Oncorine.

In contrast to Gendicine, Oncorine is a conditionally

replicative adenovirus.
Oncorine contains a deletion in E1B 55K region, which

restricts the virus to bind and inactivate wild-type p53 protein.

2009
Ark Therapeutics Group plc received the first commercial

GMP Certification in the EU for the manufacture of commercial supplies of gene-based medicines (Cerepro)

Cerepro is an adenoviral vector harbouring the gene for

the Herpes simplex virus thymidine kinase (HSV-tk)