Heart failure is the leading cause of morbidity and mortality in the world. Currently, most of the clinical intervention is done with the
aid of pharmacological agents such as β-adrenergic receptor (β-AR) antagonists, inhibitors of angiotensin II and aldosterone. However, these therapies are not ideal and they do are unable to used in the long-term. Therefore, a novel approach involves the genetic modification of the cardio myocytes.
For heart failure, genetic intervention involves inducing the over-expression of a particular target molecule and installing genetically modified donor cells (for example stem cells). The most common mechanism used by scientist to achieve this is through the use of viral vectors. In viral vectors, the harmful genes are removed and replaced with therapeutic genes. The damaged myocardial cells which are the target of the viral vector are infected by the virus and the virus inserts the therapeutic genes into the cell. The therapeutic gene will be used to produce a protein which the cell had not been able to produce itself and then normal function of the cell is restored.
In heart therapies, Adenoviruses are most commonly used. Adenoviruses have double stranded DNA and are common in many non-severe human infections such as the common cold. Adenoviruses are good candidates as vectors because they are easily manipulated by researchers and have a large cloning capacity. However the problem with these viruses is the fact that they can induce secondary immune responses in vivo and be killed by the body. This is one reason that clinical trials are currently disappointing.
Adeno-associated viruses (which contain single-stranded DNA) are much better candidates for gene therapy because they do not induce immunological responses from the body. In fact, this class of viruses is not responsible for any known human diseases. However, this class of virus is not as easily manipulated as Adenoviruses and they are not able to carry as many inserted genes.
Malfunctions in the handling of Ca2+ ions in the sarcoplasmic reticulum (SR) of the cardiomyocytes is one of the main characteristics of heart failure. Generally, the muscles are unable to contract as well because there is decreased Ca2+ ion content within the SR and it remains in the post synaptic cleft of the axon for a prolonged period of time. Targeting molecules involved in incorrect Ca2+ ion handling is an area of heart failure that gene therapies can be heavily involved in.
Researchers have supported this with experiments in animals in which they impaired the mitral valve of pigs by performing a picardial coronary artery infusion. After two months of gene therapy using the virus, they noticed a definite increase in cardiac function.
aid of pharmacological agents such as β-adrenergic receptor (β-AR) antagonists, inhibitors of angiotensin II and aldosterone. However, these therapies are not ideal and they do are unable to used in the long-term. Therefore, a novel approach involves the genetic modification of the cardio myocytes.For heart failure, genetic intervention involves inducing the over-expression of a particular target molecule and installing genetically modified donor cells (for example stem cells). The most common mechanism used by scientist to achieve this is through the use of viral vectors. In viral vectors, the harmful genes are removed and replaced with therapeutic genes. The damaged myocardial cells which are the target of the viral vector are infected by the virus and the virus inserts the therapeutic genes into the cell. The therapeutic gene will be used to produce a protein which the cell had not been able to produce itself and then normal function of the cell is restored.
In heart therapies, Adenoviruses are most commonly used. Adenoviruses have double stranded DNA and are common in many non-severe human infections such as the common cold. Adenoviruses are good candidates as vectors because they are easily manipulated by researchers and have a large cloning capacity. However the problem with these viruses is the fact that they can induce secondary immune responses in vivo and be killed by the body. This is one reason that clinical trials are currently disappointing.
Adeno-associated viruses (which contain single-stranded DNA) are much better candidates for gene therapy because they do not induce immunological responses from the body. In fact, this class of viruses is not responsible for any known human diseases. However, this class of virus is not as easily manipulated as Adenoviruses and they are not able to carry as many inserted genes.
Malfunctions in the handling of Ca2+ ions in the sarcoplasmic reticulum (SR) of the cardiomyocytes is one of the main characteristics of heart failure. Generally, the muscles are unable to contract as well because there is decreased Ca2+ ion content within the SR and it remains in the post synaptic cleft of the axon for a prolonged period of time. Targeting molecules involved in incorrect Ca2+ ion handling is an area of heart failure that gene therapies can be heavily involved in.
Researchers have supported this with experiments in animals in which they impaired the mitral valve of pigs by performing a picardial coronary artery infusion. After two months of gene therapy using the virus, they noticed a definite increase in cardiac function.
