uman cells
First case of Gene therapy:
The first gene therapy was performed on September 14th 1990, Ashanti De Silva was treated for SCID ( Severe combined immunodeficiency )Doctors removed her white blood cells, inserted the missing gene into the WBC, and then put them back into her blood stream. This strengthened her immune system. Only worked for a few months.
How it works ?
- 1. A vector delivers the therapeutic gene into a patient’s target cell
2. The target cells become infected with the viral vector
3. The vector’s genetic material is inserted into the target cell
- Functional proteins are created from the therapeutic gene causing the cell to return to a normal state
- Replicate by inserting their DNA into a host cell
- Gene therapy can use this to insert genes that encode for a desired protein to create the desired trait
Types of Viruses
- Adeno-associated Viruses
- Adeno-associated Viruses
- 1. Adeno-associated Viruses– Adeno-associated Virus- small, single stranded DNA
that insert genetic material at a specific point on chromosome 19. From parvovirus family- causes no known disease and doesn’t trigger patient immune response. It has low information capacity. A gene is always “on” so the protein is always being expressed, possibly even in instances when it isn’t needed. Hemophilia treatments, for example, a gene-carrying vector could be injected into a muscle, prompting the muscle cells to produce Factor IX and thus prevent bleeding.
- 2. Retroviruses– It is created by double stranded DNA copies from RNA. The
retrovirus goes through reverse transcription using reverse transcriptase and RNA the double stranded viral genome integrates into the human genome using integrase, it inserts the gene anywhere because it has no specific site it may cause insertional mutagenesis. Vectors used are derived from the human immunodeficiency virus (HIV) and are being evaluated for safety.
- 3. Adenoviruses- Are double stranded DNA genome that cause respiratory,
intestinal, and eye infections in humans. The inserted DNA is not incorporated into genome .and they are not replicated though Ex. Common cold
Gene therapy using an Adenovirus vector:
A new gene is inserted into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.
- Direct introduction of therapeutic DNA: Its only with certain tissue and requires a
lots of DNA.
- Creation of artificial lipid sphere with aqueous core, liposome.
- Chemically linking DNA to molecule that will bind to special cell receptors but
DNA is engulfed by cell membrane and less effective.
- Trying to introduce a 47th chromosome it exist alongside the 46 othersand this
could carry a lot of information.
Successful Gene Therapy for Severe Combined Immunodeficiency:
- Infants with severe combined immunodeficiency are unable to mount an adaptive immune response; because they have a profound deficiency of lymphocytes.
- Severe combined immunodeficiency is inherited as an X-linked recessive disease, which for all practical purposes affects only boys. In the other half of the patients with severe combined immunodeficiency, the inheritance is autosomal recessive — and there are several abnormalities in the immune system when the defective gene is encoded on an autosome.
- A previous attempt at gene therapy for immunodeficiency was successful in children with severe combined immunodeficiency due to a deficiency of adenosine deaminase. In these patients, peripheral T cells were transduced with a vector bearing the gene for adenosine deaminase.
- The experiment was extremely labor intensive, because mature peripheral-blood T cells were modified rather than stem cells, and the procedure therefore had to be repeated many times to achieve success.
- A previous attempt at gene therapy for immunodeficiency was successful in children with severe combined immunodeficiency due to a deficiency of adenosine deaminase.
- In these patients, peripheral T cells were transduced with a vector bearing the gene for adenosine