DNA that will Save the Day

Leveraging Aptamers to Build the Future of Cancer Treatment

Milind Kumar
11 min readJun 1, 2022

Abstract

I’m sure that most of us know someone in our life that has been impacted by cancer. Over 40% of us will experience it ourselves at some point in our lives, and we all probably have some knowledge of how difficult that treatment plan can be. From the almost daily hospital appointments to being off work/school full-time, and oh yeah… all those freakin’ side effects. Some days it’s vomiting, some it’s exhaustion, some neausea, some mood swings, and so much more. But what if we could go through cancer treatment, without the side effects? And what if we could treat cancer without harming our healthy cells? Introducing to you now, an idea to use DNA strands known as “aptamers” to treat our cancer patients of the future.

Table of Contents

  • 1. Background
  • 1.1 Cancer Basics
  • 1.2 Current Treatment Methods
  • 1.3 Side Effects of Current Options
  • 2. Overview of Aptamers
  • 2.1 What are Aptamers?
  • 2.2 Purpose of Their Invention
  • 2.3 What Makes Them Unique
  • 3. Applications Within Cancer Treatment
  • 3.1 How Aptamers Can Treat Tumours
  • 3.2 How they are Evolved to Do So
  • 3.3 Additional Cancer-Related Applications
  • 4. Aptamer Market
  • 4.1 Consumer Demands
  • 4.2 Current Concerns
  • 4.3 Future Development
  • 4.4 Impact
  • 5. Conclusion

1. Background

To put it as simply as possible, cancer and aptamers are basically playing a game of Link Tag together.

Now we all know how Tag works, where someone who is “it” tries to go around tagging other people so that they are now “it” and have to do the same.

But in Link Tag, instead of saying “You’re it!” after tagging someone, you would say “We’re it!” and then would both have to link arms as you try to tag other people together.

Aptamers are like the person who is “it” to start the game. They run around trying to attach to cancer cells so they can link and then kill those cells.

But before we learn more about the game of Link Tag going on in our bodies, let’s make sure we understand some of the essentials of cancer and aptamers.

1.1 Cancer Basics

Cancer is a genetic disease that can be caused by factors like errors in cell division, damaged DNA from harmful substances (ex. UV rays or smoking) or inheritance from one’s parents.

After about 6 cell mutations (which can occur from things like cells making too many/too little proteins or making abnormal proteins), a normal cell turns into cancer, of which there are over 100 different types.

Unlike normal cells, cancer cells grow even without receiving signals to grow (as well as signals to die off). As such, they invade other areas of the body very quickly and can be life-threatening in a very short amount of time.

1.2 Current Treatment Methods

The most common form of treatment right now is chemotherapy.

It is a drug treatment that uses powerful chemicals to kill fast-growing cancer cells in your body by damaging the genes inside their nuclei. Since cancer cells grow and multiply much faster than most cells, chemotherapy is a viable option.

It’s different than drugs like radiation or surgery because chemotherapy is generally administered through an IV (intravenously), allowing the drug to travel throughout the body.

There are many different types of chemotherapy, but for all these reasons mentioned above, it is usually used as an initial treatment option for most cancer patients.

1.3 Side Effects of Current Options

While for many people it has been sufficient in killing most if not all cancer cells, it does come with its fair share of disadvantages. They include:

  • Hair loss
  • Fatigue
  • Nausea and vomiting
  • Severely reduced appetite
  • Anemia (low red blood cell count)
  • Constipation
  • Weakened immune system (immunosuppression)
  • Infection
  • and many more…

All these side effects come from the fact that chemotherapy is like being in the front row at a dolphin show in Sea World. Sure you might have a great view and it will be super entertaining, but like the signs there say, you better be prepared to get absolutely soaked. 🐬 🌊

Likewise, while chemotherapy is usually pretty effective and helpful at killing cancer cells, the main downside is that they also kill healthy cells in the process, which is what causes all these different side effects.

2. Overview of Aptamers

So now that we better understand cancer and have our Link Tag analogy to refer back to for clarity, let’s get into the real superhero of the article which is the single-stranded DNA called aptamers.

2.1 What are Aptamers?

When most people think of DNA, what either comes to mind is 1) the BTS song that took over the world in 2017, or 2) the special molecules that are referred to as “the blueprint of life” as they contain the genetic info we need to grow, develop, survive and reproduce.

But let’s put the song to the side for now and get back to the more important kind of DNA (sorry K-pop fans).

In high school biology, we learned about how DNA is made up of 4 complementary bases, where Adenine (A) binds to Thymine (T) and Cytosine (C) binds to Guanine (G).

Here’s an example of what that looks like

Now usually, DNA is double-stranded and has 2 connecting pairs in a double helix shape (as shown above).

But when we look at aptamers, since they are only single-stranded, DNA will actually twist and bend itself even further to maximize the total bonded pairs. They will turn into a DNA tangle and look kinda like what happens when your earbud wires get all jumbled up.

2.2 Purpose of Their Invention

Though we haven’t yet come up with the wireless “AirPod” version of an aptamer, its invention was still a giant leap forward in medicine.

You can think of aptamers like puzzle pieces. Similar to how a puzzle piece fits only one certain spot in a puzzle, aptamers only bind to one specific molecule.

An aptamer

The reason this is so important is that if we were able to make them bind to something specific (ex. oxygen), then we could drastically improve the utility of DNA.

That is where the SELEX process comes in.

Systematic Evolution of Ligands by EXponential enrichment (SELEX) was invented in 1990 with the goal of allowing molecules to be able to recognize certain targets in the body. It is the end product of SELEX that creates the “aptamers” we want.

In this process, we use the same methods that brought us as humans to where we are today; evolution. Essentially, it is the idea of keeping the best and getting rid of the rest.

The way this would work in the development of aptamers is through directed evolution, which would begin by intentionally introducing a bunch of variants to these aptamers and then keeping only the ones that best bind to the desired target molecule (kind of like how there are a bunch of COVID variants that all behave differently).

Once we’ve performed these selection rounds where we keep only the best-performing aptamers, we can use PCR (Polymerase Chain Reaction) to create a bunch of copies of them.

We can continue to rinse and repeat this same process over and over again until we have aptamers that satisfy our end goal.

Here’s what those 3 key steps look like with more complicated terminology lol

2.3 What Makes Them Unique

By developing aptamers at scale, we will have a few massive benefits:

  • We can target them to bind to bacteria and cancer cells in the body to make treatment a lot more effective (and less damaging to the rest of the body’s healthy areas)
  • Their small size allows them to navigate through the body more easily
  • They are way more stable than antibodies since aptamers are chemically synthesized (meaning they don’t need an animal or immune response to be produced)
  • Aptamers will be a major reduction in cost for DNA synthesis, priced at around 10¢ per base pair compared to $10 per pair around a decade ago.

3. Applications Within Cancer Treatment

Since aptamers can bind to any target, cancer cells are an extremely promising partner because of how much easier it would then be to treat.

So let’s get into how exactly this game-changing operation would work.

3.1 How Aptamers Can Treat Tumours

So in our Link Tag analogy, we talked about how it's similar to how aptamers can be engineered to travel around the body trying to attach to a cancer cell and then directly link to it.

The reason aptamers are able to do this so well is that they have a very high affinity and specificity (meaning they can be very accurate at targeting a specific type of chemical property). In this case, they can be used to inhibit the receptors and growth factors in cancer development (their target of interest) from continuing to grow.

Here’s how the CD28 aptamer binds to the B7.2 ligand to reduce the signals of an immune response

3.2 How they are Evolved to Do So

So once aptamers bind to cancer, they will deliver the drugs to kill the cancerous cell by forming Aptamer-Drug Conjugates (ApDCs).

They contain 3 molecular parts that are crucial to being an effective targeted drug therapeutic: a ligand (aptamer), a drug moiety (drug), and a linker (in between the aptamer and drug).

Here is what that looks like

These ApDCs are created most easily using covalent conjugation, which is where multiple non-metal chemical compounds join to form a single one (as shown above).

In this case, drugs that are already potent and effective in treating cancer from the surface of the cells are used in this conjugation reaction to create cytotoxic agents (drugs that are poisonous to living cells).

Here are different ways to create ApDCs (we’re focused on the covalent method)

As for administering them, there is limited data on what that process will be like as there is only one approved aptamer drug so far (pegaptanib, which is used to treat liver cancer). This drug is administered through intravitreal injection (through the eye, painlessly) in small doses, but again, we’re unsure yet how other tumours could receive Aptamer-Drug Conjugates in the future.

3.3 Additional Cancer-Related Applications

Along with specifically treating tumours that have already formed, aptamers have many other potentially revolutionary abilities in healthcare. But focusing on cancer specifically, here are two other amazing use cases:

  • Treating liquid cancers by evolving aptamer-conjugated nanoparticles (ACNPs) to detect and extract cancer cells from blood
Once the cancer cells are isolated, cell profiling can be performed to basically differentiate healthy vs cancerous cells based on how much they express different proteins
  • Developing cell-SELEX (which uses whole living cells, unlike regular SELEX) to find unknown biomarkers in cancer biology/development
Those similar to SELEX in its process, cell-SELEX would be crucial in developing more accurate cancer treatment therapies

4. Aptamer Market

As an industry altogether, aptamers have been on the rise lately and will continue to be this way long into the future.

This is why…

4.1 Consumer Demands

Aptamers are one of those markets that really benefited from the pandemic as the need for COVID diagnostic kits has skyrocketed. As a result, many aptamer-based kits have been developed and used all over the world.

But the main drivers of its demand have been:

  • Its increased effectiveness: since aptamers are much shorter and smaller than antibodies, they are significantly more effective in treating sensitive brain injuries like Alzheimer’s.
  • A lack of side effects compared to other treatments like antibodies: because aptamers are non-immunogenic (they don’t cause an immune response), they are much safer than traditional antibodies
  • Scalability: there is a large potential upside here in rapidly growing aptamers, which can help more people in a faster way

4.2 Current Concerns

  1. Shortage of trained professionals — Processes like SELEX to develop aptamers are very technically challenging, so they require lots of complex equipment and expertise from researchers. Since it is a very niche market right now, the market growth is being delayed in large part due to the lack of skilled workers available.
  2. Low market acceptance — Compared to antibodies, even though aptamers can target a wide variety of molecules, there is a good amount that they simply don’t have a strong affinity towards (meaning they don’t link to them well). Also, since aptamer targets are often present in the blood, they can be exposed to many bodily processes that we don’t want to impact such as renal filtration, nuclease degradation, and spleen uptake. Since there isn’t much proof that aptamers won’t affect these processes, it is hindering their market from growing.

4.3 Future Development

Companies like SomaLogic, Inc. (US), Aptamer Group (UK), and Base Pair Technologies (IS or Iceland) are some companies innovating in the aptamer space in recent years.

Combined, the 3 of them have raised over $200 million in venture capital funding to further their research and acquire lab equipment for testing.

Since aptamers can be used both as therapeutics as well as diagnostic tools, there is a lot of interest in their potential. Below are all the different aptamer drugs that are in clinical trials:

Aptamer drugs currently in clinical trials

4.4 Impact

For a market that is projected to reach around $350 million within the next 5 years, and one that has grown by 17% year over year, it will definitely be a part of mainstream cancer treatment moving forward.

And it won’t be too long before aptamers are as well known in the cancer community as something like chemotherapy is for us today.

5. Conclusion

Aptamers are a diamond in the rough when it comes to the future of cancer treatment. While they aren’t talked about too much, if they are developed at scale, they will take the world by storm in the coming years.

With them being more effective than current treatment methods with fewer side effects and greater applications, it will be a no-brainer to make the switch.

But as for the patient experience, I can’t even imagine from my own cancer story how beneficial a treatment option like this would be.

Imagine if you could be treated for cancer without having your healthy cells also impacted. Imagine if you weren’t always exhausted, vomiting, and sick during your treatment. Imagine if you never had to lose your hair or have your muscles get super weak.

This is what the future of cancer treatment might look like with an aptamer-based solution!

If you prefer to consume this topic through video, here’s one I made that goes over it in a more concise way

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Deuces!

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