Targeted Gene Therapy can Potentially Treat Chronic Lung Disease


Researchers from Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center has devised a new strategy to treat inherited/monogenic diseases (emphysema) by lung targeted gene therapy.

The focus of the research was finding an alternative approach to treat Alpha-1-antitrypsin deficiency (AATD). AATD is one of the most common and important cause of emphysema. Emphysema is a progressive, long term, chronic, lung diseases caused by the lack of AATD and that result in single gene mutation that damages air sacs or alveoli causing morbidity and mortality.

emphysema pathogenesis

Figure 1. Pathogenesis of emphysema (photo credit:

AATD is a genetic condition that results in very negligible or lack of alpha-1 antitrypsin (AAT) in the blood. Approximately 1 in 2,500 individuals suffer from AATD.

AAT protein is made in the liver and later released in bloodstream. AAT helps the lungs to function normally and protect from any kind of damage. Lack of AAT causes severe breathing difficulty and damage of alveolar sacs.

function of AAT gene

Figure 1. Function of AAT (photo credit:

Each individual has two copies AAT gene received from each of the parent. Healthy individuals have two normal copies of AAT. Depending upon the number of damaged copies of AAT present in the patient, the severity of the disease is determined.

Individuals with two damaged copies of the gene are incapable of producing sufficient alpha- 1 antitrypsin, which causes severe symptoms like chronic emphysema and ultimately death.

AAT gene alteration consequences emphysema

Figure 2. Consequences of alterations within the gene AAT for function of AAT-protein (photo credit:

The standard protocol of treatment for AATD patients includes weekly infusion of AAT protein by intravenous technique. Not only the weekly treatment is an expensive one but also invasive and inconvenient. Therefore, researchers tried to find the alternative approach to the standard treatment by evaluating whether delivering a normal copy of gene to increase the levels of AAT protein can improve the genetic condition in AATD individuals.

The researchers introduced a normal copy of gene recombinant adeno-associated virus (AAV) vectors in experimental mice model. The significance of these vectors are their target specificity.

By this technique, AAV/8 was administered through intratracheal pathway and the pulmonary transgene expression was observed for 52 weeks. It was observed that AAT protein levels had increased within the epithelial lining.

In addition to this, the study demonstrated that more than one cell types in the liver and lungs are affected by the in vivo delivery and the severity of the emphysema has decreased in the mice model. Thereby, the study concluded the significance of AAV based targeted gene therapy approach in treatment of emphysema. The findings of the research were published in the journal “Molecular Therapy – Methods & Clinical Development.

Andrew Wilson, corresponding author and MD, assistant professor of medicine at BUSM and a physician in the department of pulmonary, allergy, sleep & critical care medicine at BMC stressed on the fact that in near future there is definitely a huge prospect for transgenic therapies.

Andrew Wilson said “These results support direct transgene delivery to the lung as a potential alternative approach to achieve the goal of developing a gene therapy for AATD.”

There is still a long road ahead before the experimental concept is introduced to the patients but the innovative technique is definitely a start of a low cost, target specific treatment.

Featured Image: Emphysema. Damage to the air sacs in lungs. Chronic Obstructive Pulmonary Disease. © designua (Stock Photo ID: 77342837)

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