Background
Inspiration
Our story with rhinosinusitis started from personal experience. Some of our close relatives and friends suffer from this disease and its devastating impacts. In fact, this is not a rare phenomenon. On social platforms, we collected numerous help-seeking posts from chronic rhinosinusitis patients, who detailed their discomfort and exchanged symptom relief tips in their posts. However, the abundance of pleas contrasts sharply with the scarcity of professional advice—none of the posts received replies mentioning any drug capable of curing this disease. Consequently, patients endure significant suffering without access to viable treatment options. Moreover, on social media platforms, which are typically saturated with information, there is a striking scarcity of content related to chronic rhinosinusitis—be it news updates, or general discussions. Given the severity and societal impact of this disease, it appears it has not received the attention it deserves. We have long hoped to change this situation but we lack inspiration and don’t know where to start.
To our delight, two papers published in Nature earlier this year provided a breakthrough. They revealed GZMK as a promising biomarker and therapeutic target for chronic rhinosinusitis.[1]
Based on this, we are considering whether it is possible to develop a diagnostic and therapeutic strategy for chronic rhinosinusitis.
Integrity Identification
In the initial stages of our project topic selection, we conducted a comprehensive duplication check to ensure proper acknowledgment of all individuals and organizations potentially related to our project. Our research mainly focused on important topics such as rhinosinusitis treatment strategies, protein de novo design algorithms, and protein binder development. Through systematic literature reviews, analysis of statistical data from official sources, and evaluation of industry trends via corporate disclosures, we studied prior achievements made by iGEM teams, enterprises, and research institutions, etc. The results confirmed our project’s novelty with almost no overlapping initiatives. All referenced contributions have been appropriately credited. We hereby reiterate our gratitude to every individual and team that supported our work.
In-depth Investigation
To better answer these questions, we intend to conduct in-depth research to further understand chronic rhinosinusitis. This investigation is expected to enhance our comprehension of the impact of chronic rhinosinusitis and the current status of its diagnosis and treatment, thereby helping us define the value of our project. Our research will primarily involve literature reviews using the PubMed database, industry analysis, and participation in interviews with both patients and medical practitioners in this field.
Prevalence of chronic rhinosinusitis
According to our research, chronic rhinosinusitis has an estimated prevalence of 8% in China, meaning that approximately 107 million individuals have CRS. Expanding our vision to the international landscape, chronic rhinosinusitis is also highly prevalent worldwide, with an estimated prevalence of 10.9% in Europe, 16% in the United States, and 6.95% in Korea.[2]
Symptoms and negative impact of chronic rhinosinusitis
Chronic rhinosinusitis is characterized by persistent inflammation of the nasal mucosa and paranasal sinuses that lasts for at least 12 weeks, typically accompanied by the formation of nasal polyps within the nasal cavity. Patients are often burdened by a range of symptoms such as persistent nasal congestion, loss of smell, rhinorrhea, facial pressure or pain, and postnasal drip.[3]
In clinical practice, the most prominent symptoms of rhinosinusitis typically include initial rhinitis, thick yellow-green nasal discharge, headache, and symptoms persisting for over ten days.
As a result, patients often endure a state where their condition, while not life-threatening, is debilitating and severely compromises their quality of life, posing physical and psychological burden on patients. [2]
Also, chronic rhinosinusitis represents a global health burden with significant epidemiological impact. The disease burden includes frequent clinical visits, productivity loss, and socioeconomic costs. A study targeting 49 adult patients receiving Omalizumab treatment revealed that 46.9% of the participants reported personal costs of €11-€50 per hospital visit, with some incurring over €1,300 annually.[4]
Existing diagnosis approaches for chronic rhinosinusitis and their limitations
Currently, doctors determine the disease based on the patient's symptoms first and then confirm rhinosinusitis via objective indicators. They first perform an initial check by simply opening the nasal passage to observe for pus or swelling. If the situation is unclear, they then rely on nasal endoscopy for a clearer examination. For suspected but non-typical cases, a CT scan is considered for confirmation, as it clearly reveals inflammation inside the sinuses.
Through conversations with patients, we have summarized the current diagnostic landscape for chronic rhinosinusitis and their attitudes towards it.
- Only clear nasal discharge and nasal obstruction are observed in the early stage of the disease, which makes it hard to distinguish it from a common cold or rhinitis. As a result, patients with rhinosinusitis often seek medical attention only when they experience noticeable physical discomfort. By this stage, the disease has typically progressed to the middle or advanced stages. This delay causes patients‘ unnecessary suffering and damage that could have been avoided, while also making treatment much more complicated.
- Although detection technology like CT scan continues to advance, they generally have low acceptance among patients. More seriously, CT is ineffective for detecting silent lesions, such as those in the sphenoid sinus, which lack obvious nasal secretions. As for nasal endoscopy, it involves distressing mucosal injury, and results are relatively unreliable.
- The overall diagnostic process is often cumbersome, involving multiple follow-up visits and trips to different specialist clinics. This is a issue notably highlighted by the patients we interviewed.

Existing treatment approaches for chronic rhinosinusitis and their limitations
Multiple treatment options exist for chronic rhinosinusitis, including corticosteroid therapy, saline irrigation, functional endoscopic sinus surgery, as well as monoclonal antibody biologics such as Dupilumab, Omalizumab, Mepolizumab etc. In clinical practice, a cross-sectional survey of 78 ARS members revealed that off-label nasal steroid irrigations and dupilumab are the most commonly used when treating chronic rhinosinusitis with nasal polyps.[2]
According to our interview with Dr. Li, the primary goal in treating eosinophilic rhinosinusitis is to control inflammation to reduce recurrence. To achieve this, physicians first prescribe corticosteroid nasal sprays such as mometasone furoate, fluticasone propionate, or budesonide. For patients with severe symptoms, in addition to topical steroids, saline nasal irrigation and biologic therapies like dupilumab and omalizumab are used. In particularly severe cases, surgical intervention may be necessary, including sinus incision for pus drainage and correction of sinus anatomy to improve ventilation.
Based on our research findings and interviews, we have compiled a list summarizing current common treatment approaches for chronic rhinosinusitis. Despite their prevalence, these therapeutic strategies have many disadvantages that can be improved.
Brief Introduction | Defects | |
---|---|---|
Corticosteroids | It is a first-line therapy for ECRS, reducing nasal mucosal inflammation and decreasing nasal polyp size. Its therapeutic efficiency has been clinically proven and it is used globally. |
1. Potential side effects: Long-term topical use in nasal cavity may lead to nasal mucosal atrophy and bleeding. Systemic use carries risks of bone density loss and compromised immune function.
2. Possibility of recurrence. |
saline irrigation | It effectively clears secretions and reduces inflammatory mediators. Its beneficial effects on postoperative recovery has been confirmed. | As an adjunctive therapy, it cannot achieve a cure for rhinosinusitis. |
endoscopic sinus surgery | It removes nasal polyps and restores sinus ventilation. | High postoperative recurrence rate |
biologics | These drugs are developed based on understanding disease pathogenesis, offering certain precision advantages. |
1. It requires prolonged development timelines and substantial research investment, therefore it is relatively expensive.
2. Its potential side effects include conjunctival inflammation and headaches. |
Traditional Chinese Medicine | Chinese acupuncture emerged as the strategy consistently perceived to be both the most effective and minimally adverse. Post-treatment observations showed resolution of nasal obstruction and epistaxis, accompanied by marked mitigation of sinusitis manifestations. | However, it still needs further investigation to determine whether this approach is actually effective. |
In addition, through targeted research and interviews, we have gathered the latest authoritative guidelines from diverse sources. This has enabled us to build a comprehensive, globally-informed understanding of current chronic rhinosinusitis diagnosis and treatment methods.
Through in-depth background research, we have found that chronic rhinosinusitis indeed imposes enormous health and economic burdens on individuals, families, communities, and society as a whole. However, current diagnostic methods often lack timeliness, and treatment strategies are not sufficiently precise—both presenting significant limitations. This reinforces the scientific problem our project aims to address: we intend to fully leverage the dual role of GZMK as an early diagnostic marker and a promising therapeutic target for chronic rhinosinusitis, in order to achieve early detection and precise treatment of the disease.
Our aspiration extends far beyond simply developing a test strip or medication. More importantly, we hope our efforts can bring small but meaningful changes to patients' lives. Also, we hope our efforts can serve as a bridge of understanding between the public and patients. We hope more people will learn about and prevent this disease, and we also hope that the suffering of rhinosinusitis patients will finally "be understood."
Reference
[1] Lan F, Li J, Miao W, Sun F, Duan S, Song Y, Yao J, Wang X, Wang C, Liu X, Wang J, Zhang L, Qi H. GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases. Nature. 2025 Feb;638(8050):490-498. doi: 10.1038/s41586-024-08395-9. Epub 2025 Jan 15. Erratum in: Nature. 2025 Feb;638(8052):E45. doi: 10.1038/s41586-025-08712-w. PMID: 39814882; PMCID: PMC11821540.
[2] Liu Z, Chen J, Cheng L, Li H, Liu S, Lou H, Shi J, Sun Y, Wang D, Wang C, Wang X, Wei Y, Wen W, Yang P, Yang Q, Zhang G, Zhang Y, Zhao C, Zhu D, Zhu L, Chen F, Dong Y, Fu Q, Li J, Li Y, Liu C, Liu F, Lu M, Meng Y, Sha J, She W, Shi L, Wang K, Xue J, Yang L, Yin M, Zhang L, Zheng M, Zhou B, Zhang L. Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis. Allergy Asthma Immunol Res. 2020 Mar;12(2):176-237. doi: 10.4168/aair.2020.12.2.176. PMID: 32009319; PMCID: PMC6997287.
[4] Dungan L, Little F, O'Connor N, Cox F. The patient perspective on use of Omalizumab in the in-hospital setting. Ir J Med Sci. 2025 Jun;194(3):793-795. doi: 10.1007/s11845-025-03978-5. Epub 2025 Jun 25. PMID: 40560316; PMCID: PMC12276100.
[5] Subspecialty Group of Rhinology, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Subspecialty Group of Rhinology, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association. [Chinese guidelines for diagnosis and treatment of chronic rhinosinusitis (2018)]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2019 Feb 7;54(2):81-100. Chinese. doi: 10.3760/cma.j.issn.1673-0860.2019.02.001. PMID: 30776860.
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