Nanobodies – antibodies’ tiny cousins – have tremendous potential as versatile and accessible alternatives to conventional antibodies, scientists say.
A new system developed by researchers at Rockefeller University and their collaborators promises to make nanobodies dramatically more accessible for all kinds of research.
Antibodies, in charge of recognising and homing in on molecular targets, are among the most useful tools in biology and medicine.
Nanobodies can do the same tasks, for example marking molecules for research or flagging diseased cells for destruction, said researchers.
Antibodies are defencive proteins deployed by the immune system to identify and neutralise invaders.
But their power can be harnessed in other ways as well, and they are used in biology and medicine for visualising cellular processes, attacking diseased cells and delivering specific molecules to specific places.
Like their larger cousins, nanobodies can also be used for these tasks, but their small size makes nanobodies much easier to grow in bacterial factories.
They can also access hard to reach places that may be off limits to larger molecules.
“Nanobodies have tremendous potential as versatile and accessible alternatives to conventional antibodies, but unfortunately current techniques present a bottleneck to meeting the demand for them,” said study author Michael Rout, head of the Laboratory of Cellular and Structural Biology.
“We hope that our system will make high-affinity nanobodies more available, and open up many new possible uses for them,” Rout said.
The team generated high-affinity antibodies, those that are capable of most precisely binding to their targets, directed against two fluorescent proteins that biologists often use as markers to visualise activity within cells: GFP and mCherry.
“The key was to figure out a relatively fast way of determining the genetic sequences of the antibodies that bind to the targets with the greatest affinity. Up until now obtaining these high-affinity sequences has been something of a holy grail,” said Brian Chait, Camille and Henry Dreyfus Professor and head of the Laboratory of Mass Spectrometry and Gaseous Ion Chemistry.
The study was published in the journal Nature Methods.