Did you know negative stain EM can be used to characterize the native conformations of your therapeutic?
Our team contributed to the recent study from Novartis, “A novel interleukin-10 antibody graft to treat inflammatory bowel disease” by using negative stain EM to investigate the native conformations of an engineered IL-10 antibody-graft therapeutic (GFT-IL10M), a potential therapeutic for Inflammatory Bowel Disease (IBD).
Although the structure of the GFT-IL10M could be solved using x-ray crystallography, the conformation was influenced by the packing of the crystal lattice, making negative stain an important complementary technique in order to understand changes to the flexibility of IL-10 in the grafting format.
The study suggests that the anti-inflammatory profile of GFT-IL10M is due to the increase in flexibility, which leads to a more selective signaling across different cell types. The engineered therapeutic also exhibits an improved half-life, further contributing to its therapeutic potential.
Michael DiDonato, Carolina Turk Simpson, Todd Vo, Mark Knuth, Bernhard Geierstanger, Joanna Jamontt, David H. Jones, John W. Fathman, Donnie DeLarosa, Tobias Junt, Damien Picard, Ulrike Sommer, Morten Bagger, Eric Peters, Shelly Meeusen, Glen Spraggon, A novel interleukin-10 antibody graft to treat inflammatory bowel disease, Structure, Volume 33, Issue 3, 2025, Pages 475-488.e7, ISSN 0969-2126, https://doi.org/10.1016/j.str.2024.12.010.
