By: Aiman Dhiloon, Isha Masood, Ayesha Umair
Synthetic Biology
Corn that resists pests. Bacteria that eat plastic. Yeast making environmentally sustainable, cheaper rose oil. Synthetic biology is the new frontier of science giving new abilities to organisms, which is any living thing, from the smallest viruses and bacteria to plants and animals. How do scientists do this? The answer lies in changing an organism’s genetic code, which are the DNA sequences that provide instructions to make living things.
Sometimes, researchers make entirely new pieces of DNA to give an organism a certain ability. Other times, they will take part of one organism’s DNA and insert it into another living thing to create something totally new. For example, scientists can take a gene that makes jellyfish glow, put it into a tree, and create a glowing tree!
Synthetic biology brings together many different areas, including biology, engineering, and sociology. All of these fields can be combined and applied to many areas of our lives, including producing materials that are environmentally friendly, creating new medicines, and improving food and agriculture. What if we used synthetic biology to make a vaccine?
Neglected Tropical Disease
Neglected tropical diseases (NTD) are a group of diseases that are caused by tiny living things such as bacteria and viruses (1). Approximately 1 billion people suffer from NTDs (2)!
So who do NTDs exactly impact? NTDs mainly affect people who live in tropical areas where the weather is hot and humid (3). These diseases are often caused by germs that grow in dirty water and places and generally impact people who live in areas with less sanitary living conditions. As such, NTDs are exacerbated in less developed areas where people have less access to clean water and healthcare (4).
NTDs can spread through vectors or be transmitted from animal reservoirs (5). Vectors are tiny creatures that can carry germs that can make people sick, such as mosquitos, ticks, and flies. When these insects or animals carrying these disease-causing germs bite a human, they can cause them to be sick. Some NTDs also have “animal reservoirs”, which means that these tiny living vectors can live inside bigger animals such as pigs, which can transfer the germs to humans who come into contact with them (5).
Two common NTDs are cysticercosis and echinococcosis, which affects 2.7 million and 2.5 million people, respectively (6). These two NTDs are caused by tiny worms, called tapeworms, that live inside our intestines and can grow to several meters. Echinococcosis is caused by a worm called echinococcus that lives in the stomachs of dogs or other animals. If you accidentally swallow the eggs of echinococcus, they can grow into fluid-filled sacs called cysts, that target our lungs or liver (7). Meanwhile, cysticercosis is caused by tiny worms called Taenia solium, which are found in undercooked pork. If someone eats undercooked pork and accidentally swallows the eggs of the worm the eggs can grow into cysts in our brains or muscles. These cysts can cause health problems such as fatigue, blindness, and seizures.
AAVPs and AAVP Vaccines
What if we can make a vaccine for these NTDs with viruses? Usually, we consider viruses to cause disease in humans, but they actually can infect lots of different things, including bacteria. Scientists can classify these viruses according to what type of thing they infect. For example, some viruses called adeno-associated viruses infect humans, while bacteriophages are viruses that infect bacteria. Viruses are very specialized to the organism that they infect, meaning that a phage would not be able to infect a human cell (8).
As for vaccines, it’s also important to know that viruses, like all pathogens, can be recognized by our body’s immune system. The immune system sees them as tiny flags that signal danger and moves to fight off these pathogens. If scientists and doctors can expose the body’s immune system to these tiny flags, without exposing them to the actual pathogen to avoid causing harm, then the immune system can learn how to fight it off earlier without risking any harm. Like so, vaccines are like a training ground for our immune system to help fight off pathogens easily the next time it encounters them (8).
So how do we use these viruses in a vaccine? Scientists can change virus genes so that instead of causing harm, they can lead to benefits. A student-led research team called McMaster SynBio is working on a vaccine using these principles. Specifically, bacteriophages’ genes can be changed to show the tiny red flags normally associated with a disease like cysticercosis and echinococcosis. This bacteriophage can be combined with an adeno-associated virus with harmful genes removed. Because adeno-associated viruses normally infect human cells, this allows this combination called adeno-associated virus phage (AAVP) to be effective in humans (8). Ultimately, this AAVP showing NTD red flags can train the human body against the diseases as a vaccine.
References:
Molyneux D. Neglected tropical diseases [Internet]. Community eye health. U.S. National Library of Medicine; 2013 [cited 2023Mar24]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756642/
Neglected tropical diseases quick facts [Internet]. National Institute of Allergy and Infectious Diseases. U.S. Department of Health and Human Services; [cited 2023Apr5]. Available from: https://www.niaid.nih.gov/research/neglected-tropical-diseases-quick-facts#:~:text=An%20estimated%201%20billion%20people,from%20at%20least%20one%20NTD
CDC. CDC - Neglected Tropical Diseases - Diseases [Internet]. www.cdc.gov. 2019 [cited 2023 Mar 24]. Available from: https://www.cdc.gov/globalhealth/ntd/diseases/index.html
World Health Organization. Neglected Tropical Diseases [Internet]. www.who.int. 2021 [cited 2023 Mar 24]. Available from: https://www.who.int/news-room/questions-and-answers/item/neglected-tropical-diseases
World Health Organization. Neglected Tropical Diseases [Internet]. www.who.int. [cited 2023 Mar 24]. Available from: https://www.who.int/health-topics/neglected-tropical-diseases#tab=tab_
Aung AK, Spelman DW. Taenia solium taeniasis and cysticercosis in Southeast Asia [Internet]. The American journal of tropical medicine and hygiene. U.S. National Library of Medicine; 2016 [cited 2023Apr5]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856625/
Taeniasis/cysticercosis [Internet]. World Health Organization. World Health Organization; [cited 2023Apr6]. Available from: https://www.who.int/news-room/fact-sheets/detail/taeniasis-cysticercosis
Hajitou A, Rangel R, Trepel M, Soghomonyan S, Gelovani JG, Alauddin MM, Pasqualini R, Arap W. Design and construction of targeted AAVP vectors for mammalian cell transduction. Nat Protoc. 2007;2(3):523-31.