Increasing Efficacy of Gene Therapy | 02 Aug 2022

Why in News?

Recently, a study titled “Secretion of functional α1-antitrypsin is cell type dependent” has been published, which shows that the Efficacy of Gene Therapy can be increased by changing protein regulation networks in the body, helping treat genetic diseases.

What is Gene Therapy?

• Gene therapy is a way to treat genetic diseases by correcting the source of the error in a patient’s DNA (Deoxy-ribo Nucleic Acid).
• Gene therapy techniques allow doctors to treat a disorder by altering a person’s genetic makeup instead of using drugs or surgery.
• A harmless viral or bacterial vector is used to carry a corrective gene into a patient’s cells, where the gene then directs the cell to produce the proteins necessary to treat the disease.
• Muscle cells are a common target because gene therapies injected into the muscle are more accessible than introduction into the body by other routes.
• But muscle cells may not produce the desired protein as efficiently as needed if the job the gene instructs it to do is very different from the one it specialises in.

What are the Findings?

• Effectiveness of Gene Therapy:
  • Developed a strategy to use a harmless version of an adeno-associated virus as a vehicle to deliver AAT (Alpha-1 Antitrypsin) gene therapies into the body via injection, allowing for sustained release of the protein over several years.
    • AAT is a condition in which liver cells are unable to make adequate amounts of the protein AAT.
    • It results in a breakdown of lung tissue that can cause serious respiratory problems, including the development of severe lung diseases such as chronic obstructive pulmonary disease (COPD) or emphysema.
  • Adding a molecule called suberoylanilide hydroxamic acid, or SAHA, helps muscle cells make AAT at a production level more like that of liver cells.
    • Proteostasis is the process that regulates proteins within the cell in order to maintain the health of both the cellular proteome and the organism itself.
    • Proteostasis involves a highly complex interconnection of pathways that influence the fate of a protein from synthesis to degradation.
  • Adding SAHA or similar proteostasis regulators to gene therapies can help increase the effectiveness of these treatments for many genetic diseases.
    • Patients are usually treated by receiving AAT via infusion. It requires patients to either make regular trips to the hospital or keep expensive equipment at home for the rest of their lives.
  • Replacing the faulty gene that causes AAT shortage in the first place can be a boon for patients.
    • Current gene therapies inject the AAT-producing gene into muscle.
• Implications:
  • Increasing the protein production of muscle cells can potentially improve vaccine immunity.
  • Adding a protein homeostasis enhancer to the cell could optimize protein yield and increase the effectiveness of the drug.
    • Many drugs are derived from natural sources that rely heavily on a given cell’s protein production capabilities.
    • But many of these drugs use cells that aren’t specialized to make large amounts of protein.
  • Ways to improve the cellular machinery behind protein homeostasis can help delay aging and open many new doors for treating a wide range of diseases.

Source: DTE