De novo developed protein binders mimicking Interferon lambda signaling

Area of Science:

• Biotechnology
• Immunology
• Molecular Biology

Background:

• Cytokines, such as type 3 interferons (IFN-λ), play crucial roles in immune responses.
• IFN-λ signaling is mediated by binding to a receptor complex involving IL-28R1 and IL-10R2.
• Developing non-antibody protein binders offers alternative tools for studying and modulating cytokine functions.

Purpose of the Study:

• To design and select novel non-antibody protein binders that mimic the signaling of IFN-λ1 (IL-29).
• To create bifunctional binders capable of simultaneously engaging both IL-28R1 and IL-10R2.
• To evaluate the functional activity of these binders in relevant cellular assays.

Main Methods:

• Utilized yeast display, a directed evolution technique, for the development of protein binders.
• Designed bifunctional binders to target the extracellular domains of IL-28R1 and IL-10R2.
• Assessed binder functionality by measuring JAK/STAT pathway phosphorylation and gene expression in human cell lines.

Main Results:

• Successfully developed bivalent protein binders that mimic IFN-λ1 signaling.
• Demonstrated that these binders activate the JAK/STAT signaling pathway.
• Confirmed induction of IFN-λ1-responsive genes by the engineered binders.

Conclusions:

• Engineered bifunctional protein binders provide a novel approach to mimic cytokine signaling.
• These binders can be used as research tools to study cytokine biology and cell behavior modulation.
• Offers an alternative to natural interferons for receptor activation studies.