Simultaneous Treatment of Viral and Bacterial Otitis Media Using Plant Natural Products
使用植物天然产品同时治疗病毒性和细菌性中耳炎
基本信息
- 批准号:10310502
- 负责人:
- 金额:$ 14.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-01 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:Active SitesAcuteAffectAlkaloidsAnabolismAnti-Bacterial AgentsAntibiotic ResistanceAntibioticsAntimicrobial EffectArtemisininsAuditory PhysiologyBacteriaBacterial Antibiotic ResistanceBacterial InfectionsBerberineBiochemistryBiologicalBiological AvailabilityBiological TestingBiologyCell Membrane PermeabilityCellsChargeChemicalsChildChild HealthChildhoodChinchilla (genus)CollaborationsComplexDevelopmentDiagnosisDiseaseDrug Delivery SystemsDrug resistanceEarEar DiseasesEffectivenessEngineeringEnhancersEnzymesExhibitsFormulationFutureGelGoldensealHealthHigh PrevalenceHuman bodyHydrogelsHydrophobicityIn VitroInfectionInvestigationIsoquinolinesKnowledgeLeadLeftLiquid ChromatographyLiquid substanceMedicinal PlantsMethodologyMicrobeModelingModificationMolecularNatural ProductsOpioidOtitis MediaPathway interactionsPermeabilityPersonsPharmaceutical PreparationsPharmacologic SubstancePlantsPreparationProductionPropertyRecurrenceResearchResistanceSiteSite-Directed MutagenesisSpeech DevelopmentStructureSystemTechniquesTemperatureTestingTherapeuticThickTissuesTreatment EfficacyTreatment outcomeTympanic membraneTyrosineUniversitiesViralVirusVirus DiseasesWorkYangYeastsantimicrobialbasebiomaterial compatibilitychemical functionchemical synthesiscytotoxicitydesignexperiencein vivoinnovationinsightknowledge basemethicillin resistant Staphylococcus aureusmicrobiomemiddle earmolecular sizenovelpathogenic bacteriapermanent hearing lossreconstructionscaffoldscreeningside effectsynthetic biologytreatment duration
项目摘要
1 Project Summary
2 Otitis media (OM) is a major child health burden. It is the most commonly diagnosed pediatric disease and the
3 #1 reason for antimicrobial prescription to US children. Moreover, 62% of children with OM demonstrate viral
4 infections in their middle ear, to which antibiotics are ineffective but prescribed nonetheless. The widespread use
5 of systemic antibiotics against a disease of such high prevalence and recurrence is believed to breed antibiotic
6 resistance. To treat viral and bacterial infections simultaneously, we will design and synthesize sophisticated
7 plant natural products (PNPs) and their derivatives with no known drug resistance,. The state-of-the-art synthetic
8 biology pipeline that we pioneered will enable the optimization and scalable production of antimicrobial PNPs
9 with enhanced permeability and antimicrobial efficacy. The novel PNP compounds will be delivered locally into
10 the middle ear using a proven hydrogel, which is an easy-to-apply liquid at room temperature and gels quickly
11 and firmly upon contacting warm tympanic membrane (TM). Chemical permeation enhancers inside the gel can
12 overcome the impermeable barrier of the TM and bring the PNPs into the middle ear. We have demonstrated
13 that a single application of the hydrogel formulation provides enough antibiotics for a 7-day treatment, eradicating
14 the infection in a chinchilla OM model.
15 The current application attempts to completely eliminate antibiotic usage in this prevalent childhood disease and
16 to mitigate OM-related drug resistance by using a stand-alone therapy that treats both bacterial and viral
17 infections. It focuses on the production and modification of berberine, an alkaloid derived from medicinal plants.
18 Berberine has demonstrated antimicrobial effects against Gram-positive and -negative bacteria including MRSA
19 and has shown antiviral properties against multiple viruses. This work will leverage our experience in PNP
20 biosynthesis to reconstruct a biosynthetic pathway in yeast for berberine production. We will incorporate diverse
21 tailoring enzymes (e.g., halogenases) and modified precursor molecules to produce modified berberine
22 derivatives that are difficult to achieve by conventional chemical synthesis. The therapeutic efficacy and
23 biocompatibility of the modified berberine derivatives will be tested using an established chinchilla OM model.
24 The knowledge and techniques developed in this project will provide new insight into overcoming the biological
25 barriers in the ear via molecular design and new treatments for acute and recurrent OM. The focus on berberine
26 is based on its known antimicrobial effect, and the general methodologies are applicable to other PNPs that
27 could treat ear diseases beyond OM.
1个项目摘要
2中耳炎(OM)是儿童健康的主要负担。它是最常见的儿科疾病,
3给美国儿童开抗菌药处方的头号原因。此外,62%的OM儿童表现出病毒感染
4中耳感染,抗生素对这些感染无效,但仍开了处方。广泛使用
对于如此高的发病率和复发率的疾病,使用系统的抗生素被认为会滋生抗生素
6抗性。为了同时治疗病毒和细菌感染,我们将设计和合成复杂的
7未知抗药性的植物天然产物(PNPs)及其衍生物。最先进的合成材料
8我们首创的生物流水线将使抗菌PNPs的优化和规模化生产成为可能
9具有更强的渗透性和抗菌效果。新的PNP化合物将在当地运送到
10使用久经考验的水凝胶,这是一种在室温下易于涂抹的液体,可以快速凝胶。
11,并在接触温鼓膜(TM)时牢固。凝胶内的化学渗透促进剂可以
12克服TM的不渗透障碍,将PNPs带入中耳。我们已经证明了
13单次使用水凝胶制剂就能提供足够的抗生素进行7天的治疗,根除
14在龙猫OM模型中的感染。
15本申请试图完全消除这种流行的儿童疾病中抗生素的使用,并
16通过使用同时治疗细菌和病毒的独立疗法来减轻OM相关的耐药性
17例感染。它专注于黄连素的生产和修饰,小黄碱是一种来自药用植物的生物碱。
黄连素对包括耐甲氧西林金黄色葡萄球菌在内的革兰氏阳性和阴性细菌均有抗菌作用
19,并显示出对多种病毒的抗病毒特性。这项工作将利用我们在即插即用方面的经验
20生物合成在酵母中重建黄连素生产的生物合成途径。我们将结合不同的
21剪裁酶(如卤素酶)和修饰的前体分子以生产修饰的黄连素
22个常规化学合成难以实现的衍生物。治疗效果和疗效观察
23将使用已建立的龙猫OM模型来测试修改后的黄连素衍生物的生物兼容性。
在这个项目中开发的知识和技术将为克服生物
通过分子设计和治疗急性和复发性OM的新方法,在耳朵中设置25个屏障。黄连素的研究重点
26是基于其已知的抗菌作用,一般方法适用于其他PNPs,
27例可以治疗耳部疾病,而不是OM。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SIJIN LI其他文献
SIJIN LI的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SIJIN LI', 18)}}的其他基金
Simultaneous Treatment of Viral and Bacterial Otitis Media Using Plant Natural Products
使用植物天然产品同时治疗病毒性和细菌性中耳炎
- 批准号:
10115426 - 财政年份:2020
- 资助金额:
$ 14.7万 - 项目类别:
Simultaneous Treatment of Viral and Bacterial Otitis Media Using Plant Natural Products
使用植物天然产品同时治疗病毒性和细菌性中耳炎
- 批准号:
10530599 - 财政年份:2020
- 资助金额:
$ 14.7万 - 项目类别:
相似海外基金
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Research Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Standard Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 14.7万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 14.7万 - 项目类别:
Operating Grants