هل يمكن جعل الهيبارين غير ضروري من خلال استغلال قوة البعوض؟

أدوية تجلط الدم

Managing blood clotting is very important for medical professionals. We discussed previously how synthetic platelets could be used to تحفيز emergency clotting in case of trauma in our article “قد تصبح المواد الحيوية الاصطناعية حاسمة في حالات الصدمات الطارئة”.

It can be equally important in other medical situations to منع clotting, for the treatment of heart attacks and unstable angina, to angioplasty, dialysis care, surgeries, and other procedures.

Traditionally, this is managed with heparin, an almost 100-year-old medical product, which is produced from pigs and cows.

However, a more advanced anti-clotting agent could arrive soon, thanks to researchers at Duke University and the Children’s Hospital of Philadelphia.

من البعوض إلى الطب

In a scientific publication titled “أبتاميريات الهيرودينات كمثبطات EXosite-ACTive site (EXACT) انتقائية وقابلة للعكس“ 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. العامل المضاد للتجلط في اللعاب يرتبط بسطح بروتينات التجلط في الدم.
2. يدخل إلى جوهر البروتين لتعطيل آليات التجلط أثناء تغذية البعوض.

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 “أبتامير” – which is a small nucleic acid strand – to bind to the blood’s thrombin protein.

المصدر: 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).

المصدر: Nature

تحكم مثالي

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.

بحوث إضافية

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.

شركات الأبتامير

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. مجموعة الأبتامير (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.

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.

المصدر: Aptamer Group

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

المصدر: Aptamer Group

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

• تطوير اختبار IHC
• اختبارات نشاط الإنزيم
• اختبارات حيوية الخلايا
• تحليل التفاعل المتقاطع
• تقييم الزوج
• اختبارات فعالية العلاج الجيني

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. توست بيوساينسز

The company specializes in DNA synthesis, باستخدام أساليب التصغير من صناعة أشباه الموصلات, saving time and money for researchers.

It is also working on creating تخزين بيانات قائم على DNA that could be used to safeguard data independent from electronic systems.

يسمح لنا هذا التصغير بتقليل حجم التفاعلات بمقدار مليون مرة مع زيادة الإنتاجية بألف مرة، مما يتيح تصنيع 9,600 جين على شريحة سيليكون واحدة على نطاق كامل.

المصدر: Twist Biosciences

In يناير 2023, 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.