Affitins: Ribosome Display for Selection of Aho7c-Based Affinity Proteins

Kalichuk, Valentina; Kambarev, Stanimir; Béhar, Ghislaine; Chalopin, Benjamin; Renodon-Cornière, Axelle; Mouratou, Barbara; Pecorari, Frédéric

doi:10.1007/978-1-4939-9853-1_2

Cited by 6 publications

(1 citation statement)

References 23 publications

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“…Our present strategy to enhance the transport of biologics across the intestinal barrier relies on Nanofitins targeting the LepR (anti-LepR Nanofitins), which offer a combination of protein robustness, modularity, and tunable specificity. These small single-chain binding proteins of 7 kDa, devoid of cysteine residues, are derived from the naturally hyper thermostable protein Sac7d [ 25 , 26 ], or more generally from the Sul7d family [ 27 ]. They can be custom-engineered for high specificity and affinity toward a target, as already demonstrated against a variety of biological targets [ 28 , 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Enhancing Oral Delivery of Biologics: A Non-Competitive and Cross-Reactive Anti-Leptin Receptor Nanofitin Demonstrates a Gut-Crossing Capacity in an Ex Vivo Porcine Intestinal Model

Masloh,

Chevrel,

Culot

et al. 2024

Pharmaceutics

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Biotherapeutics exhibit high efficacy in targeted therapy, but their oral delivery is impeded by the harsh conditions of the gastrointestinal (GI) tract and limited intestinal absorption. This article presents a strategy to overcome the challenges of poor intestinal permeability by using a protein shuttle that specifically binds to an intestinal target, the leptin receptor (LepR), and exploiting its capacity to perform a receptor-mediated transport. Our proof-of-concept study focuses on the characterization and transport of robust affinity proteins, known as Nanofitins, across an ex vivo porcine intestinal model. We describe the potential to deliver biologically active molecules across the mucosa by fusing them with the Nanofitin 1-F08 targeting the LepR. This particular Nanofitin was selected for its absence of competition with leptin, its cross-reactivity with LepR from human, mouse, and pig hosts, and its shuttle capability associated with its ability to induce a receptor-mediated transport. This study paves the way for future in vivo demonstration of a safe and efficient oral-to-systemic delivery of targeted therapies.

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