Nov 8, 2022

Biological lasso: Enhanced drug delivery to the brain


In a study recently published in the journal Nature Biomedical Engineering, researchers from Kanazawa University use a method called “lasso-grafting” to design therapeutics with enhanced longevity and brain penetration


Overview of the press release

Cell growth and repair are stimulated by biomolecules known as cytokines and growth factors. Unfortunately, delivering adequate concentrations of these molecules to the brain for treating neurological conditions like Alzheimer’s disease is challenging as they are either cleared out of the blood very quickly or do not penetrate neural tissue effectively. A research team led by Kunio Matsumoto and Katsuya Sakai at Kanazawa University in collaboration with Junichi Takagi, Osaka University and Hiroaki Suga, the University of Tokyo has now used a technique called “lasso-grafting” to design molecules that replicate growth factors with longer retention in the body and brain penetration.

This study depicts a novel strategy of inducing the effects of growth factors and cytokines with enhanced retention in brain tissues. What’s more, based on the macrocyclic peptides and antibodies selected, this technique can be applied to imitate several growth factors. “Thus, lasso-grafting enables the design of protein therapeutics with the desired physicochemical stability and controllable pharmacokinetics, as well as the rapid engineering of antibodies for multiple functionalities,” suggest the researchers.


Image : 1. Lasso-grafting to design molecules that mimic growth factors with longer retention and brain penetration. (a) A pharmacophore sequence of Met receptor-binding macrocyclic peptide (aMD4; shown in red) was inserted into the loops (coloured balls) of human IgG1 Fc protein. (b) Lasso-grafting Fc yields Met agonists with extended half-life in the body. (c) Lasso-grafting Fc of an anti-TfR antibody yields Met agonists with blood-brain-barrier (BBB) penetrance.


Professor Hiroaki Suga (Department of Chemistry, Graduate School of Science, The University of Tokyo) have contributed to this research.

To read the full press release, please visit the website of Nano Life Science Institute, Kanazawa University.


Publication details

 Journal Nature Biomedical Engineering
Designing receptor agonists with enhanced pharmacokinetics by grafting macrocyclic peptides into fragment crystallizable regions.


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