Gene therapy is a technique that can be used to insert a functional allele of a gene into an individual with a genetic disorder. There are various methods and vectors that can be used to carry out gene therapy. Despite having the potential to treat genetic disorders, gene therapy also has ethical problems that must be addressed.

Gene therapy

Definition

Gene therapy is a technique that can be used to insert a functional allele of a gene into an individual with a genetic disorder. The expression of the inserted allele should produce a functional protein which should cure the genetic disorder. The method of gene therapy used will depend on the cause of the genetic disorder.

Example

If the genetic disorder is caused by two recessive alleles, like cystic fibrosis, then a functioning dominant allele can be inserted. If the genetic disorder is caused by a dominant allele, like Huntington's disease, then it can be silenced or inactivated.

Somatic gene therapy

Definition

Somatic gene therapy involves inserting a functional allele of a gene into a cell that contains a defective allele of the gene. This method of gene therapy requires a vector to deliver the functional allele to the individual's body cell.

Note: Somatic gene therapy only impacts the individual's genome and the changes will not be passed to their offspring.

Liposomes

Liposomes are small phospholipid vesicles that can be used as vectors for somatic gene therapy.

Example

Liposomes can be used to treat cystic fibrosis patients that lack a functional CFTR gene.

Biology; Manipulating genomes; KS5 Year 12; Gene therapy: somatic, germ line and ethics

1.	A functional allele is packaged into a liposome. The liposomes are put into an inhaler. The inhaler acts as a nose spray for cystic fibrosis patients.
2.	The liposomes will pass through the membrane of the epithelial cells lining the respiratory tract.
3.	They can pass through the nuclear envelope and insert the functional allele into the patient's genome.
4.	The patient's cell will then transcribe and translate mRNA (4.)* that produces a functional CFTR protein. This will produce a functional transmembrane chloride ion channel (5.).*
6.	However, the epithelial cells are replaced every two weeks and the production of abnormal transmembrane chloride ion channels will resume. Therefore, this treatment must be carried out regularly.

Viruses

Viruses are also used as vectors for somatic gene therapy. The process through which they work is explained below.

1.	Cells that carry the defective gene are removed from the affected patient.
2.	A healthy version of the human gene is inserted into a viral vector. *Note:* The viral vector has been edited so it is unable to cause disease.
3.	The edited virus enters the cells that were removed from the patient and inserts the functional allele into the cells.
4.	The modified cells are injected back into the patient.
5.	The modified cells can now carry out their normal function inside the patient's body.

However, there are issues surrounding the use of viral vectors in gene therapy.

Viruses can cause an immune or inflammatory response in a patient even though they have been edited.
Patients can develop immunity against the viral vector which can impede further treatment.
The virus could insert in the wrong place. If this occurs in a gene that regulates the cell cycle then cancer could arise.

Example

In the late $1990s$ , gene therapy was developed to treat 'bubble-boy' syndrome. Some children showed dramatic improvement, but $3$ - $6\ years$ later others developed leukaemia and died.

Artificial chromosomes

Research is being carried out to explore the idea of inserting artificial chromosomes into the a patient that would exist alongside their natural chromosomes.

Germ line gene therapy

Definition

Germ line gene therapy involves changing the genome of gametes or zygotes. Therefore, unlike somatic gene therapy, this method will alter the genome of the patient's offspring. This method also carries the risk of incorrect insertion.

Note: Due to the ethical issues surrounding its use, germ line gene therapy is illegal.

Ethics

There are many ethical arguments for and against the use of gene therapy. These are explained below.

For	Against
It could prolong the lives of those suffering from genetic disorders.	The technology could be easily exploited.
It could also improve the quality of life for those suffering from genetic disorders.	The different methods carry a lot of risks, including the risk of developing cancer as a result of incorrect insertion.
Using germ line therapy would mean that people suffering from genetic disorders could ensure their children do not suffer from the same disorder.	Gene therapy is very expensive so some argue that this money should be spent on other treatments.

Learn with Basics

Length:

Unit 1

DNA: structure, genes and chromosomes

Unit 2

Gene therapy and gene editing

Jump Ahead

Optional

Unit 3