While the term “Drug Delivery systems” may be unheard of they are a constant in our everyday lives. Whether it’s a pill or an injection, the purpose of them remains the same – transport drugs into, or throughout the body. While many may believe that the current methods of drug delivery–transdermal, oral, and intravenous–are satisfactory and seem to be a quick fix to most of our bodily problems, the issue arises in the fact that our body is too vast and complex a vessel for all its issues to be treated by these methods. What is the blood-brain barrier, and how does it stand in the way of delivering medicine for diseases such as Alzheimer’s, Epilepsy, and Parkinson’s disease?
Enter Viruses. While they may be known as evil entities due to our preconceived notions, their abilities transcend our presumptions, and they may be the key to developing effective, and more targeted drug delivery systems.
Viruses are small infectious agents that can enter the body and deliver genetic material into the cells. These very qualities make it the most viable candidate to deliver genes to previously unreachable parts of the body. How is this done, you may ask? By the intervention of scientists, ofcourse! Their tiny form and ability to enter cells requires genetic engineering to carry therapeutic substances to specific cells in the body, which is done by a process known as Viral vector engineering.
Viral vector engineering is the process of making an infectious virus into a non-infectious viral vector, by removing the genes that make it disease-causing. In their place, a therapeutic gene, (a functional version of the faulty ones causing the disease this viral vector is meant to cure) is inserted, thus ensuring that the virus can no longer replicate and harm the host. In this process, a crucial step is picking the right virus to engineer, examples of viruses that can be used are Adeno-associated virus ( AAV), due to its ability to infect non-dividing cells and its low pathogenicity, and Lentiviruses, due to their ability to insert their virus directly into the host cell’s genome, as it is a retrovirus.
While the methodology of using viruses for drug delivery systems does make sense, the advantages and disadvantages must be weighed before deciding whether or not this can be practiced in real life. The targeted delivery provided by the engineering of viruses ensures that the therapeutic agent is delivered precisely where it needs to be, which is beneficial in minimizing the side effects of certain gene therapies on healthy tissues This can be seen in oncolytic virotherapy, in which viruses such as the Herpes Simplex Virus (HSV) are modified to infect and kill the cancer cells directly. A modified HSV (known as T-VEC) has been approved for the treatment of melanoma, showing just how revolutionary viruses can be in the form of a drug delivery system. Moreover, viruses possess a natural talent for invading cells, which improves the efficiency of transporting medicine, as this ability is not possessed by non-viral methods like liposomes or nanoparticles. Gene therapies are also already being successfully transported by viruses to cure genetic diseases such as hemophilia, in which viruses deliver the genes missing for clotting factors, and Leber’s congenital amaurosis, which is treated by the transport of a viral-based therapy, Luxturna, (voretigene neparvovec).
However, there are certain threats. The uncertainty of the immune system’s response to viral vectors being used is a challenge–since there is always a chance that the immune system may recognize it as a foreign body and neutralize it even before it can deliver the medicine to its desired location. The presence of pre-existing immunity to common viruses such as adenoviruses also limits the use of different viruses, as the immune system is already primed and ready to attack. Additionally, the chance of insertional mutagenesis with retroviruses such as lentiviruses, which can insert their DNA into the genome of the host cell, requires consideration– if this integration appears near an oncogene, the chance of causing cancer is high, which was a catastrophic problem in the gene therapy trials for X-linked severe combined immunodeficiency, in which this integration led to many children developing leukemia.
Engineering viral vectors, more specifically adeno-associated viruses (AAVs) and lentiviruses, for genetic material injections, are becoming more effective. One such direction that is receiving a lot of focus is improving the targeting of specific cell types by changing or otherwise modifying, viral capsids—structures that encapsulate the viral genome to shield it. For example, scientists are developing capsid variants that enable lower doses to decrease the risk of immune response and have fewer side effects.
Looking forward, the future of viral vector engineering incorporates innovations that will improve better design of viral capsids by application of machine learning, improved efficiency of delivery, and cheaper manufacturing. In a disease like Leber’s congenital amaurosis, these advancements, in all likelihood, can treat this disease, potentially curing a genetic disorder after a single administration.
Viral vectors are rapidly becoming the most powerful weapon in drug delivery systems, especially gene therapy. Although such problems as immune responses, manufacturing costs, and ethical concerns do exist, the research that is still going on is finding solutions to these problems. The future of viral vector gene therapy via the improvement of targeting, dosage control, and the potential to treat complex diseases such as cancer or genetic disorders is very promising.
Avni Goswami
About the author: Hi My name is Avni Goswami and I’m a 16-year-old student at Lancers International School with big dreams of becoming a doctor. I’m passionate about biology and human sciences, and I love diving deep into the complexities of the human body. Driven and curious, I strive for excellence in everything I do, and I’m always eager to learn something new. My goal is to combine my knowledge and empathy to make a difference in the world through medicine.
2 Comments
Well written!!
Proud of you avni
A very thought provoking and insightful read!