Cystic Fibrosis Gene Therapy: A Potential Cure?

Cystic Fibrosis Gene Therapy: A Potential Cure?

In recent years, advancements in gene therapy have sparked hope for treating various genetic disorders, including?cystic fibrosis,?a life-threatening disease affecting thousands of people worldwide.

With the potential to provide a cure, gene therapy for cystic fibrosis has become an increasingly promising field of research, raising the question: could cystic fibrosis gene therapy finally offer a way to conquer this debilitating disease?

Did You Know??

You may carry genes associated with inherited conditions and not develop the condition but may pass it to your children. Learn more:

Overview Of Cystic Fibrosis

Cystic fibrosis is a genetic disorder caused by mutations in the?cystic fibrosis transmembrane conductance regulator (CFTR) gene.?

The?CFTR?gene contains the instructions for making the CFTR protein expressed in the airway epithelial cells.?

When there is a mutation/change in the genetic instructions, the production or function of the CFTR protein may be affected.

The mutations in the?CFTR?gene can result in no protein, not enough protein, or the protein being made incorrectly.?

Whilst the CFTR protein is expressed in many internal organs, the significant effect of such mutations is on the respiratory, gastrointestinal, and reproductive tracts.

The critical function of CFTR protein is ion transport (the movement of salt and water in and out of your cells).

Abnormal ion transport leads to thick viscous secretions in the airways, infection,?inflammation, and eventually irreversible?lung damage.?

The lungs and digestive system become clogged with mucus, making breathing and digesting food hard.?

There is currently no treatment that halts the natural progression of the disease.

All available successful therapies merely slow the rate of decline in clinical conditions.

Gene therapy offers great hope for the treatment of genetic diseases/disorders.

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What Is Gene Therapy?

Gene therapy?or gene transfer, or gene replacement, is a technique that modifies a person's genes to treat or cure disease.?

Gene therapy can do the following:

  • Replace a disease-causing gene with a healthy copy of the gene?
  • Inactivate a disease-causing gene that is not functioning properly

Cystic fibrosis gene therapy?works by placing a new, correct version of the?CFTR?gene into the cells in a person's body.?

Types Of Gene Therapy

Two types of gene therapy have shown the potential to treat this condition.

In?integrating gene therapy, a piece of?DNA?containing a functional?CFTR?gene would be delivered to an individual’s cells.?

The new copy of the?CFTR?gene would then become a permanent part of their?genome, which is the entire set of genetic instructions in every cell.?

An advantage of integrating gene therapy is that it is permanent for the cell's life.?

This means that a person with cystic fibrosis might have to receive gene therapy only once or a few times in their life.?

A disadvantage is that there may be limited control over where the new copy of the?CFTR?gene integrates into the genome.?

This means integrating gene therapy could have undesirable side effects, such as increasing?cancer risk.

In?non-integrating gene therapy, a piece of DNA with a correct copy of the?CFTR?gene is provided to an individual's cells.

Here the DNA remains separate from the genome and is not permanent.?

Even though the newly introduced gene does not become part of the genome, the cell can still use the new copy of the?CFTR?gene to make normal CFTR proteins.

A major advantage of the non-integrating gene therapy approach is that it does not disrupt the entire genome.

That means the risk of side effects, including cancer, is low.?

A disadvantage of non-integrating gene therapy is that it is not permanent.?

The effect of the gene therapy might last only for several weeks or months and need to be treated repeatedly for it to be effective.

Classes of?CFTR?Variants Treated With Gene Therapy

Over 360 variants or changes in the?CFTR?gene can cause the condition.

Recently, these variants have been categorized into seven classes based on CFTR protein dysfunction and/or?gene expression.

  • Class I are protein production variants that result in no functional CFTR protein, with roughly 22% of patients harboring at most minuscule one?mutant allele.
  • Class II are protein processing variants that create?misfolded CFTR protein and reduced expression?on the cell membrane to function.?
  • Class III are gating variants that?impair CFTR gate opening?and encompass roughly?6%?of patients.
  • Class IV results in defective ion channel conduction. Approximately 6% of CF patients harbor this variant.?
  • Class V is?insufficient protein variants, resulting in reduced CFTR at the surface membrane, capturing?5%?of patients.
  • Class VI affects the?stability of CFTR, which causes a reduction in membrane retention, and?5%?of CF patients harbor at least one allele of this variant.
  • Class VII affects?CFTR?mRNA expression resulting in no mRNA?and includes large deletions such as the dele2,3(21 Kb) mutation.

How’s Gene Therapy For Cystic Fibrosis Done?

Gene therapy for cystic fibrosis is done by replacing the genetic mutation with a “correct version” of the?CFTR?gene.

Although the mutant copies of the?CFTR?gene would still be there, the correct copies would allow cells to make normal CFTR proteins.

An integrating gene therapy known as CAR-T therapy has already been approved to treat patients with a few types of leukemia and lymphoma.?

Several gene delivery methods exist to introduce a therapeutic gene or gene targeting.

CF gene therapy research has tested both non-viral and viral delivery vectors.

Current Status Of CFTR Gene Therapy

Scientific breakthroughs in the past ten years have accelerated advances in gene therapy.

Integrating gene therapies to treat CF is being tested in the lab, and a clinical trial to test the safety of this approach in people with CF could happen in the next several years.

Despite these advances, currently, available drugs do not treat around 10% of CF patients.

It has also been found that?existing CTF modulators are not well tolerated by eligible patients, causing many of them to stop treatment midway.

Current Challenges For Gene Therapy

Gene therapy comes with a set of challenges that need to be overcome for the process to be effective.

Some of them include the following:

  • Delivering the new gene to the?CORRECT?cell.
  • Turning on the gene by overcoming cellular blocks that try to shut down genes displaying unusual activity.
  • Successfully evades the immune system since the new genes may be considered “foreign” by the body.
  • Ensuring that the new gene doesn’t interfere with the functioning of the other existing genes.

Summary

  1. Cystic fibrosis is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.?
  2. Gene therapy is developed as a novel treatment for cystic fibrosis and involves the transfer of correct copies of desired DNA to the target site.?
  3. Gene therapy is a technique that modifies a person's genes to treat or cure disease.?
  4. During gene therapy for cystic fibrosis, the mutated gene is replaced with the correct version of the?CFTR?gene.
  5. Despite several advances in gene therapy, currently, available drugs cannot treat around 10% of cystic fibrosis patients.
  6. Current challenges in gene therapy include the risk of introducing a new gene into the wrong cell, interference with other genes, and gene shutdown.

References

First appeared in https://www.xcode.life/carrier-status/cystic-fibrosis-gene-therapy-a-potential-cure/

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