모기의 힘을 활용해 헤파린을 구식으로 만들 수 있을까?

혈액 응고 약물

Managing blood clotting is very important for medical professionals. We discussed previously how synthetic platelets could be used to induce emergency clotting in case of trauma in our article “합성 생체재료가 응급 외상 상황에서 중요한 역할을 할 수 있다”.

다른 의료 상황에서도 prevent clotting, for the treatment of heart attacks and unstable angina, to angioplasty, dialysis care, surgeries, and other procedures.

전통적으로 이는 돼지와 소에서 추출한 거의 100년 된 의료 제품인 헤파린으로 관리됩니다.

하지만 듀크 대학교와 필라델피아 어린이 병원의 연구원들 덕분에 보다 진보된 항응고제가 곧 등장할 수 있습니다.

모기로부터 의학까지

In a scientific publication titled “Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors“ and accepted by Nature, the researchers created a synthetic molecule mimicking one found in mosquitoes.

Blood-sucking organisms like mosquitoes have anti-clotting agents in their saliva. More precisely, all blood-sucking organisms use the same 2-step mechanisms:

1. 침 속의 항응고제가 혈액 내 응고 단백질 표면에 결합합니다.
2. 그들은 단백질 내부로 들어가서 모기가 먹는 동안 응고 메커니즘을 비활성화합니다.

Using these animals’ anti-clotting method makes sense, as it evolved independently multiple times, demonstrating its efficiency.

Once this anti-clotting mechanism was elucidated, researchers engineered an artificial molecule mimicking it, with a focus on interactions between thrombin and factor Xa in human blood. This molecule used an “앱터머” – which is a small nucleic acid strand – to bind to the blood’s thrombin protein.

출처: Biorender

By doing so, the researchers discovered that they could modulate the efficacy of the molecule by changing the length of a section of the protein (linker).

출처: Nature

완벽한 제어

The researchers also managed to create an “antidote” for the new anti-clotting molecule. This is a very important tool for its future applications in a medical setting. This way doctors can neutralize the agent at will, avoiding uncontrolled or unwanted bleeding.

This can create an anti-clotting procedure that will be safer for the patient. It will also reduce inflammation, always a good thing for patients potentially recovering from a heart attack or heavy surgery.

This method opens the way to create anti-clotting medicines that are independent of animal farming. This allows for a much more steady supply chain, with the current heparin supply highly dependent on Chinese pig farming, which was notably disrupted in recent years by the pandemic as well as porcine disease epidemics.

It should also reduce any risk of contamination from animal diseases and reduce the carbon emissions from anti-clotting production.

추가 연구

The technology used to replicate artificial mosquitoes’ anti-clotting agents could be expanded to other biochemical effects.

Aptamers could be used to bind into the enzyme’s catalytical center and can be utilized to develop an effective EXACT inhibitor.

Therefore, potent, selective, and reversible EXACT inhibitors can be created for virtually any enzyme, with or without defined exosites.

These studies foreshadow the development of a large class of highly potent and specific enzyme inhibitors that are rapidly reversible.

Furthermore, this approach in using aptamer to create high specificity in the molecular binding, while also having it fully reversible on commend, could help improve existing drugs or drug candidates that previously failed clinical trials.

Moreover, this generalizable molecular engineering approach can help resuscitate many small molecule drugs abandoned because they were not effective or selective enough on their own.

앱터머 기업

So far, aptamers have had niche usage, limiting the company specialized in this product to mostly lab diagnostic tools. This new study shows this product’s potential can go beyond and open new markets for these companies.

1. Aptamer Group (APTA.L)

The British company is a leader in aptamer development and production. It has an existing relationship with 15/20 top pharmaceutical companies and 42 partners despite a small size of only 37 employees.

이 영국 기업은 앱터머 개발 및 생산 분야의 선두주자입니다. 37명의 직원만 보유하고 있음에도 불구하고 15~20개의 주요 제약사와 42개의 파트너와 기존 관계를 유지하고 있습니다.

Its Optimer platform allows for the optimized discovery of the right aptamer for each case, whether it is therapeutics, lab measurements, or biological product manufacturing.

출처: Aptamer Group

It will be replaced by Optimer+ soon, offering more complex options for aptamer building and peptide/aptamer interactions.

출처: Aptamer Group

The company has been expanding its offer with the recent addition of:

• IHC assay development
• Enzyme activity assays
• Cell viability assays
• Cross-reactivity analysis
• Pair assessment
• Gene therapy efficacy assays

The company has seen its sales grow very quickly in early 2024 (3x compared to the year before).

Still, the company is quite far from profitable and should be analyzed with caution by investors.

2. Twist Biosciences

The company specializes in DNA synthesis, leveraging miniaturization methods from the semiconductor industry, saving time and money for researchers.

It is also working on creating DNA-based data storage that could be used to safeguard data independent from electronic systems.

This miniaturization allows us to reduce the reaction volumes by a factor of 1,000,000 while increasing throughput by a factor of 1,000, enabling the synthesis of 9,600 genes on a single silicon chip at full scale.

출처: Twist Biosciences

In 2023년 1월, the company started shipping products from its recently launched second manufacturing installation. The new factory should double Twist production capacities.

With its advanced DNA and RNA synthesis capability, Twist could quickly become a major aptamer manufacturer if the market for anti-clotting products grows.

As a “neutral” producer focused on providing the best nucleic acid sequences at the best price, it could be a manufacturing partner of choice for any pharmaceutical company looking to commercialize the discovery of the Duke University researchers.