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PAS-YNSα8
- Development stage
- Preclinical
- Lead developer
- XL-protein
- Modality
- Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes
- Administration
- Intramuscular, Subcutaneous
01
Overview
PAS-YNSα8 (also known as PAS-IFN superagonist) is a long-acting, engineered type I interferon (IFN) superagonist developed by XL-protein in collaboration with the Weizmann Institute of Science. It is designed on the backbone of a low-affinity human interferon-alpha 2b (IFNα2b) but incorporates specific mutations (H57Y, E58N, and Q61S, known as YNS) to increase its affinity for the interferon-alpha/beta receptor 1 (IFNAR1) by 60-fold, and C-terminal sequence modifications from IFNα8 to increase its affinity for IFNAR2 by 15-fold. To extend its in vivo half-life, the engineered superagonist is genetically fused with a 600-residue proline-alanine-serine (PAS) polypeptide sequence (PASylation). PAS-YNSα8 is being investigated for the treatment of inflammatory and autoimmune diseases, such as multiple sclerosis (MS), where it has demonstrated superior efficacy and a 10-fold increased half-life compared to standard interferon-beta (IFNβ) in preclinical models.
- Other names
- PAS-IFN superagonistPASylated YNSα8PASylated interferon superagonist
02
Targets
IFNAR (Immune system modulation via type I interferon receptor)IFNAR2 (Interferon alpha/beta receptor subunit 2)IFNAR1 (Interferon alpha/beta receptor 1)
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