In vivo nanobodies.

The new print issue of Nature Methods showed up, and it is rare for this journal not to have a cool technology or two in it. If you are in the life sciences, you can generally get a free subscription to this journal.

Antibodies are cool things, but also complex molecular structures. They are huge proteins composed of 2 heavy chains & 2 light chains, all held together by disulfide linkages. Expressing recombinant antibodies is not a common feat -- it is very hard to do so given the precise ratio & the folding required. Trying to express them inside the cytoplasm would be even trickier, as the redox potential won't let those disulfides form.

Camels & their kin, however, have very funky antibodies -- only a single heavy chain. I've never come across the history of how these were found -- presumably some immunologist sampling all mammals to look for wierd antibodies. Because of this structure, they are much smaller & don't require disulfide linkages. In fact, the constant parts of the camelid antibody can be lopped off as well, leaving the very small variable region, termed a nanobody.

The new paper (subscription required for full text, alas) describes fusing nanobodies to fluorescent proteins & then expressing them in vivo. Since only a single chain is needed, the nanobody coding region can be PCRed out & fused to your favorite fluorescent protein. The paper shows that when expressed in cells, these hybrids glow just where you would expect them to. The ultimate vital stain for any protein or modification! With multiple fluorescent protein of different colors, multiplexing is even theoretically possible (though not approached in this paper).

Of course, one is going to need to generate all those nanobodies. There is already a company planning to commercialize therapeutic nanobodies (ablynx). Perhaps another company will specialize in research tool nanobodies -- ideally without the nanoprofits and nanoshareprices which are all too common in biotechnology!