A New Filter Paper Technology for Flavivirus Collection, Shipping, and Analysis

用于黄病毒收集、运输和分析的新型滤纸技术

• 批准号: 9348101
• 负责人: MICHAEL E. HOGAN
• 金额: $ 90.92万
• 依托单位: GENTEGRA, LLC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-08 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9348101
• 关键词: Animals; Award; Biological; Biological Assay; Biological Preservation; Biotechnology; Blood; Blood Preservation; Caliber; California; Cellulose; Chemicals; Chemistry; Collaborations; Collection; Congenital Abnormality; Coupled; DNA; Dengue; Dengue Virus; Development; Diagnosis; Eligibility Determination; Environment; Epidemiology; Fingers; Flavivirus; Flavivirus Infections; Formulation; Funding; Geography; Goals; Heat Stress Disorders; Human; Infection; Institution; International; Lead; Legal patent; Link; Logistics; Medical; Methods; Microcephaly; Microspheres; Modeling; Molecular Epidemiology; Mutate; Mutation; Neonatal Screening; Neurologic; Nucleic Acid Amplification Tests; Paper; Pennsylvania; Phase; Plasma; Plasticizers; Population; Porifera; Preparation; Printing; Production; Protocols documentation; Public Health; RNA; RNA Viruses; Recovery; Refrigeration; Research; Research Personnel; Resources; Reverse Transcriptase Polymerase Chain Reaction; Reverse Transcription; Sampling; Shipping; Small Business Innovation Research Grant; Solid; Technology; Temperature; Testing; Travel; Tropical Climate; Viral Genome; Viral Load result; Virginia; Virus; Work; Yellow Fever; Yellow fever virus; Zika Virus; base; blood product; cryogenics; elastomeric; improved; innovation; interest; man; manufacturing scale-up; new technology; next generation sequencing; novel; novel strategies; pressure; programs; prototype; sample collection; screening; vector; vector mosquito; viral RNA

Abstract The Flaviviruses, especially Dengue, Zika and Yellow Fever have been a major public health concern for centuries in semi and tropical climates, including parts of the southern US. Presently, these viruses are the cause of more than 300 million infections per year. Global travel, alteration of the underlying mosquito vector’s geographical range, the possibility of RNA genome mutation resulting from vector changes and new environmental selective pressures all appear to have influenced the spread of Flavivirus infection to new human populations. More recently, Zika, with the proposed link to microcephaly and other neurological birth defects, has thrust into the spotlight an urgent need for an economical, international-scale screening of susceptible populations. We believe there is a critical need to develop new technology to collect, transport and recover blood or blood products containing this pervasive class of unstable enveloped RNA virus, in the complete absence of any sort of protection via refrigeration. The goal of this new technology is the recovery of intact viral genomes to support viral load and nucleic acid testing: to improve the diagnoses of Flavivirus infection and, coupled with new, now- inexpensive methods of Next Gen sequencing, to provide the real possibility of discovering how the viral genome may be mutating under selective pressure. The overarching requirement for such new sample collection and preservation technology is that it must be robust enough to preserve even the most unstable of the Flavivirus RNAs, yet inexpensive enough to support both population scale public health screening and sophisticated molecular epidemiology to detect mutational drift (via Next-Gen sequencing) while being deployable in a way that facilitates implementation in isolated, tropical, poor, susceptible populations in the complete absence of cryogenic preservation. GenTegra, in collaboration with Ahlstrom (the world-leader in medical grade filter paper for newborn screening) have recently co-developed a medical grade cellulose paper that supports long term stabilization of the DNA in blood at ambient temperature. In this Phase II SBIR, GenTegra will leverage that ongoing collaboration with Ahlstrom, coupled with our expertise in the development and implementation of the new stabilization chemistries, to develop a completely new filter paper based product for Flavivirus RNA field collection and preservation. To achieve those highly Innovative and Significant goals, we propose 3 Specific Aims, to be executed over 2 years. Upon successful completion, this program will yield a product prototype that will be ready for manufacturing scale-up and international commercial deployment. The Investigators and Research Environment among the collaborating institutions (GenTegra, ATCC, and Ahlstrom) are of international caliber with respect to delivering this (21st century) approach to paper-based biosample collection. It should be noted that, although this SBIR is purely focused on Flavivirus, the technology may be generally applicable to ambient temperature collection and transport of all RNA viruses in animals and man.

摘要 几个世纪以来，黄病毒，特别是登革热，寨卡和黄热病一直是主要的公共卫生问题 在半热带和热带气候，包括美国南部的部分地区。目前，这些病毒是导致更多 每年超过3亿人感染。全球旅行，改变潜在蚊子媒介的地理位置 范围、载体变化导致RNA基因组突变的可能性和新的环境选择性 压力似乎都影响了黄病毒感染向新人群的传播。更 最近，寨卡病毒与小头畸形和其他神经系统出生缺陷有关， 强调迫切需要对易感人群进行经济的、国际规模的筛查。 我们认为，迫切需要开发新技术来收集、运输和回收血液或血液 含有这种普遍存在的不稳定包膜RNA病毒的产品，在完全没有任何形式的 通过冷冻进行保护。这项新技术的目标是恢复完整的病毒基因组， 病毒载量和核酸检测：提高黄病毒感染的诊断，再加上新的，现在- 下一代测序的廉价方法，以提供发现病毒基因组如何 可能在选择压力下发生变异。 对这种新的样本收集和保存技术的总体要求是它必须是稳健的 足以保存即使是最不稳定的黄病毒RNA，但足够便宜，以支持这两个 人口规模的公共卫生筛查和复杂的分子流行病学，以检测突变漂移（通过 下一代测序），同时以便于在孤立的、热带的、贫穷的、 在完全没有低温保存的情况下， GenTegra与Ahlstrom（新生儿筛查用医用级滤纸的全球领导者）合作 最近共同开发了一种医用级纤维素纸，支持DNA的长期稳定， 环境温度下的血液。在第二阶段SBIR中，GenTegra将利用与 Ahlstrom，再加上我们在开发和实施新的稳定化学品方面的专业知识， 开发一种全新的滤纸基产品，用于黄病毒RNA的野外收集和保存。到 为了实现这些高度创新和重要的目标，我们提出了3个具体目标，将在2年内执行。 在成功完成后，该计划将产生一个产品原型，将准备制造 扩大规模和国际商业部署。研究者与研究环境 合作机构（GenTegra、ATCC和Ahlstrom）在交付方面具有国际水准 这种（21世纪世纪）的方法，以纸张为基础的生物样品收集。值得注意的是，尽管这一SBIR 纯粹专注于黄病毒，该技术可普遍适用于环境温度收集， 所有RNA病毒在动物和人类中的运输。