Most antibodies — those molecules that course through our blood and tissues patrolling for pathogens — are fairly hefty as proteins go. But the antibodies made by camels and sharks and their close relatives are simpler and smaller. Since their discovery in the late 1980s, researchers have learned that these antibodies pack a big punch: They can latch onto hidden parts of molecules and can penetrate tissues more deeply, enhancing their potential as therapies.
In the last decades, investigations of these diminutive antibodies have surged. Not only can they sneak into small places, they are also easy to work with — sturdier than their ordinary counterparts — and relatively cheap to make in large quantities. All these features make the antibodies promising treatments for a host of diseases, whether clotting disorders or Covid-19. Researchers are also exploring their use for diagnosing conditions such as cancer, and they’re becoming a key tool in other kinds of research, like mapping cells’ insides.
Full-size antibodies, like those of humans (left), typically have heavy protein chains (dark blue) and light protein chains (light blue). In addition to these standard antibodies, sharks and camels and their relatives make antibodies with only heavy chains (middle and right). The fragments at the antibody tips (shown in circles), called variable domains, stick to parts of pathogens or toxins, whatever substance is recognized as foreign to the body. The variable domains of sharks (VNARs, middle) and camels (VHHs, or nanobodies, right) have an extra-long fingerlike extension, called the CDR3 loop, that can reach into nooks and crannies inaccessible to a standard antibody fragment (ScFv, left).
In standard antibodies (which camels also make), the variable domains come in pairs, one from the heavy chain and one from the light chain. But the variable domains of the camelid’s heavy-chain-only antibodies are singletons. The researchers realized these solitary fragments might be able to grab onto parts of foreign molecules that conventional antibodies were too bulky to reach.
In 1993, this discovery was published and in the next year, Hamers patented the production of these camelid antibody fragments (they are also known as VHH antibodies or “nanobodies,” a trademarked term). A few years later, a different group of researchers reported that sharks also make antibodies with only heavy chains and these have an even smaller tip (these shark end fragments are called variable new antigen receptors, or VNARs).
Note - Prof Raymond Hamers - Vrije Universiteit Brussel in Brussels, Belgium. (sadly passed away 22 August 2021 - RIP)
When the primary patent expired in 2013, research investigating the antibodies really surged, and the scientists have since learned a lot about the advantages of these mini antibodies.
Unlike full-size antibodies, the fragments are stable at room temperature so there’s no need to keep them in a freezer or ship them cold. The mini antibodies of sharks can even be boiled with no effect on their function.
And while full-size antibodies require mammalian cells to be grown in a flask, which can be complicated and expensive to maintain, the fragments can be manufactured in large quantities using bacteria, saving time and money.
Here's a recent documentary on this topic...(It's about 40 min long and watch when you got some time)
In the last decades, investigations of these diminutive antibodies have surged. Not only can they sneak into small places, they are also easy to work with — sturdier than their ordinary counterparts — and relatively cheap to make in large quantities. All these features make the antibodies promising treatments for a host of diseases, whether clotting disorders or Covid-19. Researchers are also exploring their use for diagnosing conditions such as cancer, and they’re becoming a key tool in other kinds of research, like mapping cells’ insides.
Full-size antibodies, like those of humans (left), typically have heavy protein chains (dark blue) and light protein chains (light blue). In addition to these standard antibodies, sharks and camels and their relatives make antibodies with only heavy chains (middle and right). The fragments at the antibody tips (shown in circles), called variable domains, stick to parts of pathogens or toxins, whatever substance is recognized as foreign to the body. The variable domains of sharks (VNARs, middle) and camels (VHHs, or nanobodies, right) have an extra-long fingerlike extension, called the CDR3 loop, that can reach into nooks and crannies inaccessible to a standard antibody fragment (ScFv, left).
In standard antibodies (which camels also make), the variable domains come in pairs, one from the heavy chain and one from the light chain. But the variable domains of the camelid’s heavy-chain-only antibodies are singletons. The researchers realized these solitary fragments might be able to grab onto parts of foreign molecules that conventional antibodies were too bulky to reach.
In 1993, this discovery was published and in the next year, Hamers patented the production of these camelid antibody fragments (they are also known as VHH antibodies or “nanobodies,” a trademarked term). A few years later, a different group of researchers reported that sharks also make antibodies with only heavy chains and these have an even smaller tip (these shark end fragments are called variable new antigen receptors, or VNARs).
Note - Prof Raymond Hamers - Vrije Universiteit Brussel in Brussels, Belgium. (sadly passed away 22 August 2021 - RIP)
When the primary patent expired in 2013, research investigating the antibodies really surged, and the scientists have since learned a lot about the advantages of these mini antibodies.
Unlike full-size antibodies, the fragments are stable at room temperature so there’s no need to keep them in a freezer or ship them cold. The mini antibodies of sharks can even be boiled with no effect on their function.
And while full-size antibodies require mammalian cells to be grown in a flask, which can be complicated and expensive to maintain, the fragments can be manufactured in large quantities using bacteria, saving time and money.
Here's a recent documentary on this topic...(It's about 40 min long and watch when you got some time)
