• Respiratory virus infections such as Influenza, are a major threat to public health worldwide.
• The global respiratory tract infection treatment market was valued at US$ 34,276.8 Mn in 2016, and is expected to expand at a CAGR of 6.2% from 2017 to 2025.
• The current systems for studying biology and pathology of human respiratory epithelium and infection of respiratory viruses, are human lung explant and primary human airway epithelial cell culture. However, they are neither convenient nor reproducible.
• Human cancer cell lines have also been used to propagate viruses and to study virology. Although, they are unable to simulate human respiratory epithelia, thus inappropriate for evaluating pathophysiological attributes.
• Therefore, a system to model human respiratory epithelium is needed to understand the biology and pathology of human respiratory tract and assess the infectivity of emerging viruses in humans.

• The invention describes a method for generating a system to model human respiratory epithelium.
• The resultant two-dimensional (2D) and three dimensional (3D) proximal differentiated airway organoids can morphologically and functionally simulate human airway epithelium and can discriminate human-infective influenza viruses from poorly human-infective viruses. They show appreciable mucociliary differentiation.
• Beating cilia, which play essential role in human airway biology and pathology, are clearly discernible in every single organoid.
• Serine proteases, important for productive viral infection are significantly upregulated.

Advantages

• Biologically relevant, reproducible, and readily available in vitro model.
• Most mature human airway epithelium model.
• Can be expanded for a long period.
• These airway organoids allow for inter-individual comparisons.
• They can be readily modified by lentiviruses and CRISPR technologies and can be single-cell cloned.

• Modelling biology and pathology of respiratory epithelium, testing therapeutic agents and regeneration medicine.
• Predicting the infectivity of influenza viruses and assess the cross-species transmission potential of emerging influenza viruses in humans

• US Provisional Application No. 62/679,788
• Prototype available.