Prenatal Gene Therapy
The concept of Fetal Gene Therapy focuses on the addition and/or removal of xenogeneic material to the tissues and cells of a fetus in order to cure prenatal disorders through a vector. Although unsuccessful in previous years, current research and experiments have brought new life to the field. Using a vector to transport the beneficial genes to the fetus directly (when it is inside the mother), treats the somatic cells which are, essentially, the most important of their kind as they are what most of the body is comprised of. Treating these cells ensures that the child is free of genetically inherited diseases. Prenatal Gene Therapy also involves care of the baby when it is inside the womb, denoting care of the amniotic fluid (the sac inside which the baby is kept safe). A deficiency of amniotic fluid could also affect the child after it is born which could lead to birth defects, including absent organs. This involves an ex vivo treatment which is then transported to the fetus to strengthen the sac. The principal advantage to Gene Therapy is that it has the ability to cure diseases and disorders that are not completely remediable as time passes similar to cancer. Gene Therapy also has its downside, as it gives rise to an increased chance of mortality prenatally and postnatally. As time progresses and researches advances, the reliability of Gene Therapy increases and morbidity rates are decreasing.
Image 1: The entire process of Ex vivo Gene Therapy Explained
Scalzo, Stephanie. Digital image. Contemporarybiotechissues.wikispaces.com. N.p., n.d. Web.
Significant findings in the field of Fetal Gene Therapy have been known for the better part of twenty years and previously the theory of Gene Therapy was based on inserting genetic materials into the non germline cells in order to cure the disease possessed by the fetus. Among the first attempts to develop a cure for genetic disorders, was in 1997 at St Mary’s School of Medicine in London, UK in order to find the cure for cystic fibrosis. The experiment was carried out in mice by targeting the fetus at various times during the gestation period with the aid of two separate viral vectors to deliver the therapeutic genes. The findings read that the amniotic fluids present around the fetus of the mice was strengthened due to the successful attachment of the retrovirus. Since then, similar procedures have been carried out in sheep, monkeys and various other mammals with the vision of discovering an accurate, low risk prenatal remedies.
As the years have gone by, Gene Therapy has made large levels of progress, and is currently able to target large amounts of dividing cells, providing the therapeutic effect to cells more efficiently. The idea of Gene Therapy is useful as it has the ability to cure diseases that cannot be cured after birth, much like cystic fibrosis. Recent findings have shown that attempting to transport genetic material to the fetus early in the gestation period can be helpful as it can prevent the disease in the first place. Moreover, the size of the fetus is extremely important as stronger vectors can be used on feti that have been further developed to ensure a more effective treatment. In addition to the high rates of morbidity, Prenatal Gene Therapy is a highly restricted procedure and is only to be performed under certain circumstances. These circumstances include: major chances of morbidity post or prenatally, no possible cure after birth and the chances of survival and cure are high. Another important factor in Fetal Therapy is the use of vectors as they are essentially the only way of transporting the gene to the fetus. An idealness of a vector is mainly based on its efficiency and safety for the mother. An efficient vector is one that does not require many attempts to deliver the gene, which is not highly common in vectors due to the fact that it has to pass through the human body which does not provide optimal conditions for the vector to survive in. Another factor taken into consideration when choosing a vector is its ability to target the affected organ. Altogether, these factors play a pivotal role in deciding precisely the vector to be used. Over two decades of research have shown that the best vectors to use for these situations are cosmid, plasmid and lambda phages, which are bacterial viruses that provide the best results when transporting a gene. Although tremendous progress has been made, the field of Prenatal Gene Therapy is yet to be completely explored. The current practice is essentially a very small step as prenatal disorders are quite easily discoverable now, without which further research in the field would be a dead end as families would have absolutely no idea regarding how they should proceed. After overcoming this hurdle, scientists and doctors are currently working on the future of Fetal Gene Therapy and are focused on making it more widely acceptable.
Image 2: Procedures for the targeting process of vectors
Voidoinikolas, G. GIFT Model for Personalized Medicine and Surgery. Digital image. Cellr4.org. N.p., n.d. Web.
As the field of Prenatal Therapy is further explored, it is vital to determine which diseases are easily curable by it and which are not. In addition to that, certain diseases may be better treated neonatally (post birth) while some would be better cured by replacement with an already fertilized embryo which is not infected by the disease. However, predictions based off of all the findings, have given the edge to Fetal Therapy as it goes beyond treating the disease, and essentially removes the affected gene. The future of Gene Therapy will mainly be based on its ability to cure extreme diseases which are impossible to cure neonatally such as cancer. It is essential to improve the characteristics of the vector and its delivery techniques in order for the field to progress. The end goal of developed vectors would be to transport the therapeutic gene which would exterminate the affected gene for the entirety of the individual’s life, without causing an interference in the development of the individual’s other organs. The ideal vector would be different from the current ones in terms of structure and composition as it would be purely bacterial and non viral. The development of vectors also comes with a huge drawback, as it’s safety can not be determined without carrying out the procedure on a living thing, which is time consuming and could easily cause the death of the fetus. The future holds a promise, which is to discover the optimal time to inject the therapeutic gene to cure the fetus as it is definite that the procedure can not be safely carried out before mid gestation. Another factor to consider is the fetal immunity to the vector, as it would aid in discovering the optimal strength of the vector as the strength would determine the intensity which would either cause the fetus to die, or would have no effect on it. Another issue that faces Prenatal Gene Therapy involves couples who have an affected child would rather have an abortion instead of enduring treatment for their child. In the views of the general public, this idea is barely present because it is not widely accepted due to a low success rate. Scientists and Doctors would require the aid of the government in order to get this information through to the general public.
The applications of Fetal Gene Therapy reside merely in the medical field which includes restricting growth in animal feti. The sole purpose of restricting the growth is to experiment with the same subject for as long as possible. The benefit of having the same subject for a longer period of time is that more tests can be done in order to predict the effect of similar tests on humans. Another application of the treatment is in place for patients with diaphragmatic hernia as treating it would enhance the patient’s breathing capabilities and yield a lower chance of facing issues such as asthma when the child grows up. Finally, Gene Therapy, currently, is not permitted in humans unless successfully performed on multiple animal subjects. Now, as this kind of therapy is gaining popularity, it will serve as a means of educating the public in prenatal cures, which would eventually lead to lower abortion rates in mothers of all ages because they would be able to essentially decide their baby’s physical and mental capabilities.
Image 3: Prenatal Gene Therapy (Cell based vs Direct)
Mirza, Annie. Ex Vivo and In Vivo Treatment. Digital image. Slideshare.net. N.p., n.d. Web
The central focus of Fetal Gene Therapy is to cure prenatal disorders which are essentially impossible to cure neonatally. Gene Therapy uses vectors in order to transport therapeutic genes to the fetus which in turn replaces the affected gene. Initially, this concept was derived from research in cancer and congenital blindness around thirty years ago, and ever since scientists have been attempting to find the cure for every known genetic disease. The advancement of this field is mainly reliant on improving its existing characteristics such as the vectors, which are essentially the most important part of Gene Therapy. As time progresses, Prenatal gene Therapy is gaining popularity and establishing itself as a treatment that can lower the rates of abortion worldwide.