Author: Brian Caballo

Brian Caballo is a student at The Bronx High School of Science in New York City, NY. He is mainly interested in the fields of neuroscience and stem cell biology.

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Biomedical Research

Behind the Scenes of Social Situations: Why We Act The Way We Do

By Brian Caballo

Published 7:58 PM EST, Fri April 23, 2021

Introduction

Picture this: you are a student in class who had just blurted something you believed to be funny out in front of the whole class. All of your classmates burst out into laughter. In one instance, because you see others laughing with “happy faces,” you mentally perceive this as a positive occurrence, and start to get excited and laugh along with everyone else. In another instance, the complete opposite happens. Though you see everyone laughing and being entertained, you perceive this as a negative occurrence and feel like you are being ridiculed, so you start to tear up and feel offended. These two cases are meant to display how the perception of social situations may vary for different people; it all is based on previous memories, experiences, and how we view things, which is not fully consistent in all people. 

Dodge’s Social Information-Processing Model

To better understand perception and reaction to social situations, let’s take a look at one of the most widely accepted theories that have been established for social information processing: Dr. Kenneth Dodge’s Social Information-Processing (SIP) model. In this model, Dodge, describes 5 different steps that dictate how an individual acts in a given situation. 

The first step of this model is Encoding. When placed in a given situation, an individual must observe social “cues” expressed by the people around them to encode. Social cues are essentially different verbal or non-verbal signals that are shown through activity in the face, body, voice, motion. One major example is people laughing and smiling, like in the introductory example. The individual takes these cues in, and begins the interpretation process.

Following Encoding is the step of Mental Representation. When the social cues around the individual are observed and focused on, meaning is then attached to these cues. This interpretation of the cues can be positive or negative depending on how the individual views them mentally.

The next step is Response Accessing. Here, the individual physically responds to the mental representation of the previous step. Such physical responses can either be seen or unseen; smiling and crying are seen reactions, while an increase in heartbeat rate due to excitement is unseen. 

After Response Accessing is the step of Evaluation. In Evaluation, the individual must decide how they end up acting as a result of the perceived social cue. Looking back at the example in which you thought about if the whole class laughed and you began to tear up, a few options can result from this situation. You can think about storming out of the classroom, covering your face, confronting someone close to you, etc. This evaluation period can be extremely short, but it still does occur.

The final step of this model is Enactment. This is when the final action from the Evaluation step is decided upon and executed. This concludes the entire social-information processing procedure. 

It is clear that there are many steps in this social-processing and response process that are personalized to different people. Different perceptions of social cues in the Mental Representation step can be dependent on prior experiences, which may lead the individual to perceive cues a certain way. The decision making occurring in the Evaluation step can be more impulsive, based on whether the individual acts more on emotion rather than logic. That is why social situations are often unpredictable.

Action Tendencies

With Dodge’s model in mind, it is clearer to see why certain people act a certain way more often. For instance, let’s picture someone who has aggressive action tendencies; someone who is frequently on-edge and reacts negatively in many social situations. If that person was placed in the classroom situation mentioned earlier, in which they say something and get laughed at, we can infer that they would take it as teasing and have the reaction of getting upset. This can often result because that person sees the world in a certain way that is much different from others; they tend to focus on the negative and distressing cues around them, and often views situations as threatening. Furthermore, if this person is inclined to execute a negative or aggressive behavior at the end of the SIP procedure, then they may have developed a limited number of responses to social situations. Most of these responses would be violent, which then creates a largely aggressive behavioral tendency. 

How would such tendencies come to be? Such aggressiveness can be attributed to a home life that brings out violent behaviors. Perhaps the individual has a sibling that is frequently violent with actions like shoving, and the individual got accustomed to doing the same back. Therefore, the individual would get used to searching specifically for hostile cues in his household, which carries over to real-world social situations. 

Brian Caballo, Youth Medical Journal 2021

References

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Biomedical Research Health and Disease

Why We’re Addicted to Our Phones

By Brian Caballo

Published 11:02 PM EST, Mon April 5, 2021

Introduction

The development of social media has transformed into the pinnacle of human interaction in today’s world. Especially in light of this ongoing pandemic, the longing for interaction is quelled by the boundless communication that is easily executable from our smartphones. In the past 12 months alone, the number of social media users worldwide has increased by 490 million. With this new upsurge in users, there is now a total of 4.20 billion people that use social media around the world – that is over half of the world’s population! With such a large influence over modern society, it is needless to say that the time spent scrolling through social media platforms has grown as well. Especially in the teenager age group, more specifically middle and high school students, it is common to see large daily screen time spent on apps like Instagram, Snapchat, and TikTok. Too many times we tell ourselves “five more minutes” but continue to scroll through social media way past this time.

Dopamine

Why does this happen? You can blame your mindless scrolling on the hormone called dopamine. Our brain produces this chemical, and it plays an extremely significant role in motivating behavior, which is basically a push to keep doing something. Actions and behaviors that are generally regarded as beneficial to us, such as eating tasty food or having a good workout, prompts a release of dopamine so that we keep repeating them. Dopamine serves as somewhat of a “reward” for the actions we do by providing us pleasure when it gets released. Naturally, we as humans seek out more and more of that pleasure, so we keep doing the actions that give it to us. 

Our brain has four pathways for dopamine to travel through, each with different processes. Three of these pathways are associated with the reward system: the mesocortical, mesolimbic, and nigrostriatal pathways. These pathways are responsible for why we are addicted to certain actions, as they release dopamine to certain areas in our brain to give us feelings of pleasure. 

The problem with this “reward system” is that it is somewhat of a positive feedback loop. The more we do an activity that prompts a release of dopamine, the stronger the connection between that activity and dopamine release gets. This activity is then reinforced, and we likely do more of it as a result.

Dopamine and Social Media

This whole dopaminergic reward system connects to social media because of one major factor; our brains release dopamine when we are able to have social interaction. This could mean a plethora of different stimuli that we recognize as a successful social interaction. For instance, seeing someone smiling or laughing, whether that be in-person or digitally through your phone, is perceived as a sign of social interaction because it is as if you told something to that person to cause them to laugh. 

A major component of social media addiction is the notifications that pop up. Likes, comments, direct messages; all of it. In short, we are getting a huge amount of attention for little to no effort. This gives us a rush of dopamine because it is perceived as a successful social interaction by our brains. This turns into a cycle where we just keep wanting more of these notifications to feel special. 

Another facet of social media addiction is the content that we consume. With a lot of social media platforms, there is a lot of interesting, comedic, or informative content that is short. For example, let’s take a look at the platform TikTok. While the limit for TikTok videos is now 60 seconds, it used to be a 15-second maximum. The information in these brief videos can stimulate a dopamine response because we are receiving relevant content in such a short period. (This emphasis on short content length can be seen in other platforms like Twitter, which has a character limit on tweets to ensure they aren’t too long and boring.) Then, when we scroll down, we are exposed to a brand new TikTok video with brand new interesting information. This cycle continues; we are stimulated by all of the kinds of information TikTok has to offer. You may ask yourself what makes Tik Tok so addictive, and that would be the “For You Page”. The “For You Page” has an algorithm that keeps track of the types of videos that we like and interact with. The types of videos we enjoy then keep popping up, and keep us scrolling for even longer. 

Another interesting perspective on social media addiction is that we connect with everyone else, but still remain anonymous. We are able to access the social interaction and attention we crave, and at the same time, we do not have to worry about being “embarrassed” or putting ourselves out there. We can have whole conversations in the comments without exposing ourselves. Our anonymity allows us to avoid the full effects of judgement, and yet we also have the power to freely judge others. Social media gives us a newfound social power that did not exist before.

Conclusion

It is important to keep in mind that the goal of social media platforms and businesses is to make us addicted. When we are on their apps for longer, we watch more sponsored ads, we boost their ratings and thus their capabilities, and more. 

If you find yourself falling into the clutches of social media, try to remember that that is their whole intention; to keep you mindlessly stolen. Instead, try to think of other productive ways to use your time and release dopamine; exercise is a good one! Furthermore, eating well and sleeping a good amount naturally increases dopamine levels, which uplifts your mood! Don’t let your smartphone control you, you’re the one that’s in control!

Brian Caballo, Youth Medical Journal 2021

References

DataSeries – Medium. (2020, September 6). How TikTok Is Addictive. https://medium.com/dataseries/how-tiktok-is-addictive-1e53dec10867#:~:text=TikTok%20may%20be%20addictive%20if,it%20is%20short%20and%20captivating. 

Science in the News. (2018, May). Dopamine, Smartphones & You: A battle for your time. https://sitn.hms.harvard.edu/flash/2018/dopamine-smartphones-battle-time/ 

Addiction Center. (2020, November 20). Social Media Addiction. https://www.addictioncenter.com/drugs/social-media-addiction/#:~:text=When%20a%20person%20posts%20a,perpetuates%20the%20social%20media%20habit.

Dr. Kojo Sarfo. (2020, September 27). How to Stop Endless Scrolling on Social Media. https://www.kojosarfo.com/how-to-stop-endless-scrolling-on-social-media/ 

DataReportal – Global Digital Insights. (2021, January 27). Digital 2021: Global Overview Report. https://datareportal.com/reports/digital-2021-global-overview-report. 

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Biomedical Research

Hemispherectomy: Removing Half of the Brain

Introduction

The brain is a strange-looking blob of wrinkles that remains locked away in each of our skulls. No matter how unique-looking it is, it is also the reason why you can read and comprehend this article. It is impossible for one to even live without a brainstem, which is the area of the brain responsible for core functions such as breathing, heart beating, and other involuntary actions that keep our mind and bodies working. 

There are many ways that brain sections can be divided, and each part is responsible for functions that are utilized every day in our lives. One way we could look at the brain is by dividing the left and right cerebral parts, or hemispheres, and recognizing the different roles that they play. There is a clear split down the middle separating the two hemispheres.

Cerebral Hemisphere (Wikimedia Commons)

These two hemispheres execute different functions. Most generally, the left side of the brain controls the whole right side of the body, such as the right arm, right leg, etc. Thus, the right side of the brain controls the left side of the body. Similarly, information picked up from the left half of one’s field of vision goes to the right hemisphere and vice versa. 

More specific functions of the left hemisphere include speech, language, calculations, analysis, time, and more. On the other hand, the right hemisphere deals more with creative thinking, spatial ability, perceptions, and facial recognition. 

 What happens if a person ends up with only one hemisphere, meaning that only one half of their brain is present? What if I told you that there were rare cases in which half of the brain is removed intentionally to benefit the person? Bizarre, right?

Hemispherectomy

The procedure for removing, or partly removing, a hemisphere of the brain is a surgery called hemispherectomy. The formal terms for the surgery variations are “functional hemispherectomy” for when a smaller part of the brain is removed, and “anatomic hemispherectomy” which is when a full hemisphere is removed. This removed area is permanently disconnected from the rest of the brain and extracted from the head.

Why in the world would anyone have to go through such a thing? Those diagnosed with the disorder of epilepsy experience seizures, which are caused by an increase of abnormal brain activity bouncing back and forth between the two cerebral hemispheres. This brain activity travels through the corpus callosum, which is a nerve tract that connects the hemispheres and allows them to work together. Sometimes, the seizures that occur in epileptics do not respond to anti-epileptic medicine and can get worse over time if they continue to occur. At this point, the only effective solution would be to target the source of the seizures; the brain. Since the seizures are caused by bursts of brain signal activity between the two hemispheres, getting rid of one of the hemispheres would solve the problem. 

Hemispherectomies are not just done on any epileptic. First of all, it is usually performed on children and sometimes on adults. In addition to having uncontrollable seizures, patients must have seizures that mainly originate from one side of the brain, giving a strong reason to remove that whole hemisphere. Epileptics would also be a candidate if one side of the brain has a loss of neurological function from another type of injury or disorder, and removing that part of the brain prevents any further damages.

Procedure

Before the surgery, the patient has their hair shaved. In the steps leading to the surgery, the patient gets anesthetized. Hemispherectomies begin with the removal of a part of the skull to obtain access to the brain. The corpus callosum, the bridge connecting the two hemispheres, is cut to prevent any seizures from traveling to the other hemisphere. Then, areas of the brain are removed and disconnected. Afterward, the skull part is then replaced and sealed. This surgery usually takes about 6 hours with about a week of hospitalization after it finishes. Then, rehabilitation is likely necessary. 

What Happens After Hemispherectomy?

Our brains have the incredible ability of plasticity. Simply put, the brain can modify and grow itself in different areas. This ability is especially important in the case of brain disease. When one area of the brain is damaged, other areas of the brain can rewire with new synapses and essentially do the functions that the damaged area once did. New synapse connections are made to maintain homeostasis. 

Hemispherectomy is usually done in children because younger brains have higher plasticity. Therefore, the remaining parts of the brain can recover and pick up functions from the removed area thanks to this plasticity ability after the surgery is complete. 

Considering that the right side of the brain receives and controls the left side of the body and the left side of the brain manages the right side of the body, total hemisphere removal can cause some sensory issues. However, those that undergo hemispherectomy cannot be told apart from those with a full brain. It is ultimately the safer route in some cases to prevent damaging seizures and a further loss of brain function.

The brain is truly incredible, and it must be protected by the best of our abilities. 

Brian Caballo, Youth Medical Journal 2021

References

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Health and Disease

Insomnia: The Most Common Sleep Disorder

Introduction

When thinking about the most crucial functions of life, one may visualize the actions of eating food or drinking water. However, what is often overlooked but equally as important is the mechanism of sleep! The rejuvenating and recharging of the body during sleep is essential to maximize one’s health. It maintains cognitive functions, fights off disease, and repairs our body to make way for growth. While the necessity of sleep is evident, it, unfortunately, is taken for granted by many. People can form bad habits and choose to neglect their sleep. In other cases, work and school can get in the way of a good night’s sleep. On average, a young adult needs about 7-9 hours of sleep a night. When this threshold is not met over extended periods, negative effects can occur. 

Insomnia

When one’s sleep patterns or habits are changed, overall health can be negatively affected. When health is being harmed, a sleep disorder may have been developed. The most common and prominent sleep disorder is called insomnia. The disorder of insomnia is characterized by trouble falling asleep, trouble staying asleep, or waking up too early and being unable to return to sleep. When this occurs, one’s health is at stake considering that the necessity of sleep is being compromised.

Insomnia is split into two types; acute insomnia and chronic insomnia. Acute insomnia is a short-term version of the disorder, often lasting days or weeks. On the other hand, chronic insomnia occurs for much longer, around the duration of a month or more. According to a study done by the University of Pennsylvania School of Medicine in 2018, about 1 in 4 Americans experience acute insomnia each year. Fortunately, about 75% of those affected individuals were able to recover before the disorder became chronic. Why is acute insomnia so common? There are a multitude of factors behind the disorder’s development.

Causes

In most cases, insomnia develops from poor habits. Staying up late while looking at the bright screens of phones, computers, and TVs can change one’s sleep cycle due to prolonged exposure to light. A dark environment is usually beneficial to falling asleep. Furthermore, eating a hefty meal at a late time can also contribute to trouble sleeping. One may not feel truly comfortable and ready to sleep with a full stomach. 

Insomnia is also usually associated with negative thoughts and emotions that can disrupt proper sleep. Recurring, nightly concerns can elevate feelings of stress; your mind can stay active and overthinking, and thus make it hard to fall asleep. These negative emotions reappear every time you sleep, and eventually, it becomes a cycle of overthinking and not sleeping.

While insomnia can be a primary, stand-alone disorder, it is also possible that other preexisting conditions influence the development of insomnia. Disorders regarding mental health, such as depression and PTSD, can cause trouble sleeping by keeping one awake too long. Furthermore, medications like antidepressants that are meant to combat such mental health disorders can contain ingredients that make sleeping harder, like caffeine. Physical conditions and medical conditions that cause pain, inner-body discomfort, and trouble breathing also would cause difficulty with sleep.

Overall, it is clear that there are a plethora of causes behind insomnia. While not all are easily solvable, such as insomnia that develops due to other medical conditions, some treatments can have a potentially effective resolution.

Symptoms

As mentioned earlier, insomnia is usually marked by difficulty falling asleep or staying asleep. Other symptoms of the disorder include a lack of feeling well-rested after sleep, which can affect behavior and actions throughout the day due to tiredness. Insomnia can also cause a lack of concentration in school or work, as cognition would be lacking without proper sleep over time. Such factors can contribute to the development of heightened anxiety and stress oversleep and general life activities, which can even lead to depression. Overall, one’s life can be changed drastically without maintained sleep. 

Treatments

The treatments of insomnia can vary based on the root problem behind the disorder. As mentioned earlier, it is seen that insomnia frequently stems from poor habits and negative emotions regarding sleeping. One of the most effective treatments that deal with such issues is a type of therapy known as Cognitive Behavioral Therapy for Insomnia (CBT-I). It is a talk therapy that is usually done with a medical professional, but there are many options to consider on the Internet and apps. CBT-I mainly targets the bad habits surrounding one’s lack of sleep; it analyzes thoughts, behaviors, and emotions. Furthermore, it helps people control or eliminate negative thoughts and actions that keep them awake. The patient and therapist would look at and assess these habits, then change them for better sleep results. There are several parts of CBT-I, such as sleep restriction that limits the amount of time spent in bed throughout the day, and any daytime naps. Removing these habits would likely make the patient more tired during the night, and thus make sleeping easier. Another example of a CBT-I method is relaxation techniques that emphasize muscle relaxation and breathing techniques to ease an active mind, stress, and anxiety that can occur in the nighttime. Once more, CBT-I is an analysis and changing of one’s habits to influence better sleep. It is usually personalized based on each patient’s specific habits and cases, and thus the specific methods utilized can vary.

When a patient’s situation worsens, prescription medication can be an effective treatment, though it is suggested that medication is not used for extended periods. Prescription pills can induce sleep or maintain a sleeping state. Prominent examples of such medication include Eszopiclone and Ramelteon. 

Eszopiclone is a hypnotic medication, which works by being a GABA receptor agonist. GABA is an inhibitory neurotransmitter that inhibits certain brain signals and decreases activity in the nervous system, so by being an agonist, Eszopiclone can promote a decrease of nervous system activity during sleeping time. This medication particularly helps people fall asleep faster, stay asleep longer, and lessen how often they wake up during the night.

Ramelteon is a medication that serves as a melatonin receptor agonist. Melatonin is a neurotransmitter that regulates the timing of circadian rhythms and sleep in response to darkness, so by being an agonist to melatonin, sleep in the dark would likely be enhanced. As with Eszopiclone, Ramelteon medication helps people fall asleep faster, stay asleep longer, and lessen how often they wake up during the night.

Many other prescribed sleeping pills also serve as a GABA or melatonin agonist to promote better sleep quality in the same way that Eszopiclone and Ramelteon do. 

Brian Caballo, Youth Medical Journal 2020

References

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Health and Disease

SAD: Depression Influenced by the Seasons

Introduction

Depression is a disorder notoriously known for its ambiguity. It can develop in an individual at any age, from sprouting teenagers to middle-aged adults. Furthermore, there is a plethora of both long and short-term causes of depression that can amalgamate over time and contribute toward the depressive disorder. These causes can stem from hereditary, psychological, and environmental aspects in one’s life, as well as a number of other areas. When thought of, the causes of depression often regard specific cases of each patient’s individual life: instances of trauma, underlying illnesses, etc. However, this is not true for one type of depressive order in particular: seasonal affective disorder (SAD).

What is SAD?

Seasonal affective disorder is a type of depression stemming from more general environmental changes. Specifically, it is linked to the change in seasons throughout the year. The disorder will begin when a certain season begins and end when another season comes around, at about the same times every year. SAD commonly occurs when the winter season comes, and is therefore called winter depression, in which changes occur during the winter months and cease when the spring/summertime comes around. Though less frequent, summer depression can also be a possibility in individuals, which is when the disorder starts in the spring or summer and dissipates in the late fall and winter. In these seasonal periods of depression, people experience drastic shifts in behaviors and moods, up to the point where it disrupts normal thoughts and daily activities. The severity of such changes can differentiate from a minor mood swing to a true depressive disorder. 

Symptoms

Overall, SAD has many common symptoms. A major indicator is strong feelings of depression for the majority of the day, everyday. Furthermore, very clear and sudden shifts in established behaviors, like a loss of interest in activities that were once enjoyed, a lack of energy, and a lack of sleep, frequently occurs. Self-deprecating and suicidal thoughts, sluggish actions, and even physical changes regarding weight also point toward a depressive disorder. While these can be indicators of any general depressive disorder, the occurrence of the changes at only a certain time in the year during specific seasons points toward a development of SAD. 

There are several symptoms that are seen more with winter depression. Examples include oversleeping, weight gain, and decreased energy. Conversely, summer depression is associated with lack of sleep, weight loss, and increased anxiety.

Sometimes, some of these symptoms can be normal, temporary mood swings. However, if they persist for an extended duration, it is important to note such behaviors and recount them to a doctor for a diagnosis.

Causes

The inducing of SAD is the change in seasons. But what exactly does the seasonal change do to an individual to bring about such drastic effects? Research has suggested that it was mainly the changes in sunlight levels in the winter seasons. Sunlight usually controls the amount of serotonin in the body: a neurotransmitter associated with mood regulation. People with SAD may have poorer serotonin function around certain light levels, and thus have a decreased mood regulation with lower levels of light. Furthermore, the hormone melatonin can also play a role behind SAD symptoms. Melatonin regulates sleep, and research findings have shown that people with SAD can overproduce the hormone, causing oversleeping during summer depression. Overall, chemical disruption in the body, especially those that affect core aspects such as mood and sleep, can certainly push a depressive state. 

The development and effects of SAD can be amplified by other factors as well. Primarily, individuals who have family members with SAD or other types of depression can be susceptible to a higher likelihood of SAD development. Also, SAD may be more common in an individual who already has a pre-existing major depressive or bipolar disorder.

An individual’s location in relation to the equator can also affect the development of SAD. It is more common in those who live farther north or south from the equator, as there are longer summer days and darker winter days.

SAD also occurs more in women than men. Millions of people in America may suffer from the disorder without truly knowing; some people consider such actions as signs of “laziness” rather than true depression. 

Treatment

There are several methods that can be utilized in the treatment of SAD. Since the most common form of SAD is winter depression, which is usually due to changes in sunlight, light therapy can be used as treatment. There are several variations of light treatment, some involving a very bright box or a light visor that is worn like a cap on one’s head. The patient will either be exposed to the box or wear the cap for about 30-45 minutes a day during the time periods of depression, usually in the morning. These lights are about 20 times brighter than a regular indoor light, and also filter out damaging UV rays to prevent serious eye damage. Overall, it is a helpful method to provide balance to the chemicals that are affected by the winter’s lack of light. Some side effects include eye strain, sleeping problems, headaches, and fatigue.

Another form of treatment is medication. Antidepressants called serotonin re-uptake inhibitors (SSRIs) can improve the moods of patients, and can manage the serotonin disruption during winter depression by increasing serotonin levels. Another medication called bupropion can prevent seasonal depressive symptoms when taken daily. These medications can have different side effects depending on the individual.

Brian Caballo, Youth Medical Journal 2020

References

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Biomedical Research

Adeno-Associate Virus (AAV): A Virus That Benefits Lives

Introduction

Upon hearing the term “virus,” it is the common trail of thought to picture the destructive manipulation of cells through a rapid replication process. Since diseases are now able to thrive in the body’s weakened state, such dismantling of the body’s immune system can lead to pathogenesis. Long story short, this perception of a virus is attached to a negative connotation where the virus harmfully invades an organism to manipulate the metabolic equipment that resides in cells. These viruses effectively inject their DNA/RNA information into the cell and commence the production of proteins that create more replications. Such significant shifts in the cell’s activity largely disrupt homeostasis and can permanently damage the cell. The growing virus hijacks more and more cells to amass more and more copies, thus destroying tissues and eventually organs. Different viruses may target different areas. For instance, the notorious Influenza virus targets the area involving the nose, throat, and lungs. Cells that line lung airways are susceptible to viral attack, and the body pays a toll by fending the virus off and destroying any remains of the virus. This is where the common symptoms of the flu arise. Overall, viruses can generally be characterized as aggressive, damaging particles that can leave the body weak and devastated. 

However, a special type of virus exists—one that does not involve the uncontrollable hijacking of defenseless cells.

Adeno-Associated Virus Discovery

The Adeno-Associated Virus (AAV) was initially discovered around 50 years ago. Scientists Bob Atchinson, M. David Hoggan, and Wallace Rowe uncovered the new virus particles while researching the established adenoviruses, which are very common viruses that elicit symptoms of an ordinary cold. This new virus was established to be a member of the Parvoviridae virus family since it consisted of single-stranded DNA. When the basic background research of this virus was underway, it was clear that it was unique; there was a drastic difference in virus behavior that was not consistent with other adenoviruses. AAV did not replicate within a cell culture—the main function associated with a virus! Unlike many other viruses, AAV did not execute a replication spree that manipulated and destroyed cells; it simply did not replicate. It was eventually found that AAV was able to execute standard virus replication while being introduced into a cell with other adenoviruses, or “helper-viruses,” concurrently. The researchers concluded that viral pathogenesis (virus leading to disease) was not possible with this virus due to the inability of replication. 

Around 15 years after the initial discovery, more research elucidated the details of the virus’s basic genetic information. Namely, it was confirmed that the virus can manufacture up to 100,000 particles per infected cell when paired with a helpervirus. This set the path for vector research.

AAV as a Vector

With such distinct features, it was clear that this virus could be utilized in a therapy-based manner. Yet another striking aspect of the virus strain was the size of the genome. The AAV genome is extremely small and consists of around three genes. This feature, along with the previously mentioned features of non-existent pathogenesis, controllable viral replication, and general minimized risk, led to AAV’s use as a recombinant vector.  In other words, scientists sought out to use AAV to deliver non-native genetic information as a therapeutic method in patients with genetic diseases. Such a preferable genome allowed for very effective genetic editing.

Modern Gene Therapy with AAV

In modern-day AAV-based gene therapy, scientists have managed to create an efficient way of editing the virus vector to their liking. Simply put, the single strand of DNA within the virus is cut apart. The middle part of the DNA strand is removed, but the ends of the strand are left as they are necessary for gene transfer later on. New foreign DNA containing therapeutic genes is placed to fill in the strand and spliced with the two ends to join the pieces together.

Following this is the actual vector process. As mentioned previously, AAV requires the presence of another virus in order to replicate. This “helpervirus” certainly plays a role in gene therapy. Both the edited AAV vector, as well as a compatible helpervirus, are combined with a bacterium. This effectively creates what is known as a plasmid (one plasmid being the AAV vector with the bacterium, and another plasmid being the helpervirus with the bacterium), which is a genetic formation that is capable of replication and can be used to easily affect genes and gene expression. Once both plasmids are introduced to the target cell, many AAV particles are produced within the cell and thus effectively activate the therapeutic gene, which creates the protein needed to potentially resolve a disease or problem within the given tissue.

Applications

AAV therapy has already been proven to be capable of relieving the symptoms of several types of diseases and issues that have been problematic to many patients. AAV is also behind some of the very few Food and Drug Association (FDA) approved gene therapies, which means that the benefits substantially outweigh the risks. 

An example of such a therapy is “Luxturna,” an AAV-based therapy used to treat a type of retinal disease that is passed down through inheritance. Over time, blindness can result in a patient as a result of this disease. This disease involves the RPE65 gene, which normally contains the instructions to produce the RPE65 protein, a necessary protein for vision. Mutations in this gene cause a lack of RPE65 proteins, which can negatively affect the function of RPE cells that contain the proteins. These cells are responsible for photoreception, and when a large amount of RPE cells become dysfunctional, loss of vision can be imminent. 

AAV is used as a vector for delivering unmutated RPE65 genes to the RPE cells and producing the RPE65 proteins that were initially lacking. The vector is sent inside the body via eye injection. Once the vector reaches the targeted RPE cells, functional cell numbers return to normal, and vision can be restored effectively. 

Looking Forward

AAV has certainly been a breakthrough in the past and is serving as an effective therapy for problems that were considered unsolvable a few years back. For the future, it is clear that the next steps are to utilize AAV vectors as solutions to more genetic problems and diseases and to ensure that these therapies are FDA approved. With further research into AAV vectors, many diseases with temporary fixes can be treated with more effective solutions. AAV is truly quite a unique virus, and applications can certainly be maximized in the future.

Brian Caballo, Youth Medical Journal 2020

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