Approaches to Gene Therapy | Gene Therapy Techniques

We have already discussed gene therapy, its types and its risks. Now its time to read about some approaches to gene therapy or gene therapy techniques.

Gene Therapy Techniques

There are certain techniques for carrying out gene therapy. These includes:

1. Gene augmentation therapy

This therapy is used to treat diseases caused by loss of function of a gene. The diseases occur because a functioning product (protein) cannot be made by gene due to mutation.

Gene augmentation therapy
Gene augmentation therapy

Gene augmentation therapy aims at replacing a defective copy of a gene with a functioning gene. Introducing extra copies of a functioning gene may increase the amount of normal gene product to a sufficient level. This can be achieved by two different methods mentioned below.

  • Using gene editing technique to target specific DNA sequences and repair mutations directly in the DNA. The enzymes cut out the faulty sequence and replace it with a functional copy.
  • Using the SMaRT technique to targets and repairs the messenger RNA (mRNA) transcripts copied from the mutated gene.

For example, this can be used to treat loss of function disorders such as cystic fibrosis.

2. Targeted Killing of specific cells

This general approach is popular in cancer gene therapies. This therapy aims to insert a gene into a diseased cell that causes the cell to die. This can be done by either Direct cell killing or Indirect cell killing by immunostimulation.

Direct cell killing using suicide genes
Direct cell killing
  • Direct cell killing: the inserted genes(suicide genes) are expressed to produce a lethal toxin which kills the diseased cell.  Or, a gene encoding a prodrug is inserted, which increases the sensitivity to killing by a subsequently administered drug.
Indirect cell killing by immunostimulation
Indirect cell killing by immunostimulation
  • Indirect cell killing by immunostimulation: It uses immune-stimulatory genes to provoke or enhance an immune response against the target cell.

It is important to note the inserted gene is targeted appropriately to avoid the death of cells that are functioning normally.

3. Gene Inhibition Therapy

This type of gene therapy is suitable for the treatment of infectious diseases, cancer or inherited disease caused by inappropriate expression of a gene.

The aim of this therapy is to introduce a gene whose product either:

  • inhibits the expression of another gene.
  • interferes with the activity of the product of another gene.

For example, Cancer is sometimes the result of the activation of an oncogene. So, by eliminating the activity of that oncogene through gene inhibition therapy, it is possible to prevent further cell growth and stop cancer.

Gene Inhibition Therapy
Gene Inhibition Therapy

This technique can be carried out by following ways:

  • TFO Gene Therapy: It targets the DNA sequence of a mutated gene to prevent its transcription(wiki). This technique delivers short, single-stranded pieces of DNA, called oligonucleotides. These oligonucleotides bind specifically in the groove between a gene’s two DNA strands. This binding makes a triple-helix structure that blocks the DNA from being transcribed into mRNA.
  • RNA interference: It takes advantage of the cell’s natural virus-killing machinery, which recognizes and destroys double-stranded RNA. This technique introduces a short piece of RNA with a nucleotide sequence that is complementary to a portion of a gene’s mRNA transcript. The short piece of RNA attaches to its complementary sequence, forming a double-stranded RNA molecule, which the cell then destroys.
  • Ribozyme gene therapy: It targets the mRNA transcripts copied from the gene. In this technique, ribozymes are designed to find and destroy mRNA encoded by the mutated gene so that no protein can be made from it.

4. Genetically modifying immune cells

Our immune system makes large numbers of white blood cells, each of which recognizes a particular molecule (antigen) that represents a threat to the body and destroy them.

Researchers can isolate an individual’s immune cells and genetically engineer them through gene therapy to recognize a specific antigen, such as a protein on the surface of a cancer cell. When returned to the patient, these modified cells will find and destroy any cells that carry the antigen. Ultimately destroying the cancer cells.

Challenges In Gene Therapy

Gene delivery and activation: For some disorders, gene therapy will work only if we can deliver a normal gene to a large number of cells (several million) in a tissue. Targeting a gene to the correct cells is important to the success of any gene therapy treatment.

Delivering a gene to the wrong cell would be ineffective, and it could cause health problems for the patient. Even if the right cell has been targeted, the gene has to be turned on.

Immune response: Gene-delivery vectors must be able to avoid the body’s natural immune response system. An undesirable immune response could cause serious illness or even death.

The challenge here is to find a way to deliver genes without noticing the immune system. This can be done by using vectors that are less likely to trigger an immune response or by giving patients drugs to temporarily suppress the immune system during treatment.

Obstructing important genes:  Ideally, an introduced gene will continue to work for the rest of the patient’s life. The introduced gene must become a permanent part of the target cell’s genome, usually by integrating itself into the cell’s own DNA.

It is important that gene integrate itself into an appropriate location, without disrupting any another gene. If the introduced gene interferes with any important gene, it could have damaging effects like cancer and even death.

For Nerds:

SMaRT – Spliceosome-Mediated RNA Trans-splicing

TFO – Triple-helix-forming oligonucleotide

ODN – Oligodeoxynucleotide

Transcription: Process in which a particular segment of DNA is copied into RNA (especially mRNA) by the enzyme RNA polymerase.

Rakesh Barwar
Rakesh Barwar
Founder and Editor-in-Chief of The Last DNA. My passion for technology and biotechnology give rise to this awesome site. I write articles that can be easily understood by a majority of people, therefore making biotech simple and interesting!



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