Our goals

The goal of Team Siberia’s project LEAP2BRAIN is to provide a novel drug delivery system by combining the principles of living therapeutics and N2B (nose-to-brain) delivery. We have decided to demonstrate this concept on LEAP2, an endogenous antagonist and an inverse agonist of the ghrelin receptor GHS-R1a [1][2].

The levels and relative proportions of LEAP2 and Ghrelin regulate appetite and satiety, thereby influencing human eating behaviour [3]. The results of a preliminary study on the effect of the LEAP2/ghrelin ratio on mice suggest that LEAP2 may be used as a treatment of Class I and II obesity in humans [4].

In order to induce weight loss, LEAP2 must be periodically supplied directly to the brain. It has already been shown that for nasally administered proteins such delivery is possible via the olfactory and trigeminal nerves, bypassing the bloodstream and the blood-brain barrier.

We are planning to create DH5 alpha and BL21 strains of E.coli that secrete a fusion protein composed of LEAP2, Low Molecular Weight Protamine (a type of cell-penetrating peptide) and a Myc-tag.

The overall goal of our project is to provide a proof of concept for the development of living therapeutics working on the principle of nose-to-brain delivery. Another point of interest is the investigation of the effect that CPP’s have on membrane permeability to target proteins from the inside of a cell.

After iGEM, we have plans to test our system on an in vitro model to confirm the penetration of the mucosal barrier of the nasal epithelium and to test whether the delivery of the fusion protein happens either directly through neurons or via an intercellular mechanism.

Team Siberia

Danil Shchukin

Team Leader

Marina Chuprikova

Team Leader

Artemii Ivanov

Team Leader

Daria Malysheva


Alexander Vikhorev

Dry Lab

Anastasia Paramonik


Anna Skotnikova


Ulyana Shishkova

Wet Lab / Media

Evgeniy Egorov

Dry Lab


Useful links


1 – Ge X, Yang H, Bednarek MA, et al. LEAP2 Is an Endogenous Antagonist of the Ghrelin Receptor. Cell Metab.2018;27(2):461-469.e6. doi:10.1016/j.cmet.2017.10.016

2 – M'Kadmi C, Cabral A, Barrile F, et al. N-Terminal Liver-Expressed Antimicrobial Peptide 2 (LEAP2) Region Exhibits Inverse Agonist Activity toward the Ghrelin Receptor. J Med Chem. 2019;62(2):965-973. doi:10.1021/acs.jmedchem.8b01644

3 – Lu, Xuehan et al. “LEAP-2: An Emerging Endogenous Ghrelin Receptor Antagonist in the Pathophysiology of Obesity.” Frontiers in endocrinology vol. 12717544. 24 Aug. 2021, doi:10.3389/ fendo.2021.717544

4 – Gupta D, Ogden SB, Shankar K, Varshney S, Zigman JM. "A LEAP 2 conclusions? Targeting the ghrelin system to treat obesity and diabetes". Mol Metab. 2021;46:101128. doi:10.1016/ j.molmet.2020.101128