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Synthetic adenovirus libraries for vector optimization

用于载体优化的合成腺病毒文库

基本信息

批准号：
10460635
负责人：
FRED BUNZ
金额：
$ 36.84万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-20 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10460635
关键词：
Address Adenovirus Vector Adenoviruses Adopted Bar Codes Biomedical Research Capsid Proteins Cell physiology Cellular Stress Characteristics Complex Cosmids Custom DNA DNA Library DNA Viruses DNA biosynthesis Development Discipline Epitopes Frequencies Gene Delivery Generations Genes Genetic Screening Genetic Transcription Genetic Variation Genome Genomic Library Goals Human In Vitro Individual Infection Knowledge Libraries Mammalian Cell Methods Mutagenesis Mutation Nature Normal Cell Open Reading Frames Plasmids Process Production Property Proteins RNA Processing Reaction Resources Scientist Serotyping Signal Pathway System Techniques Technology Tissues Toxic effect Transgenes Tropism Tube Variant Viral Viral Genome Viral Physiology Virus base biological adaptation to stress cell type combinatorial design field study homologous recombination improved innovation interest mutant neutralizing monoclonal antibodies next generation novel recombinant adenovirus synthetic biology synthetic construct tool trait transgene delivery vector whole genome

项目摘要

Synthetic adenovirus libraries for vector optimization Adenoviruses have been extensively utilized to address fundamental questions in biomedical research. These small DNA viruses rely on numerous host proteins for their own replication, and have been useful probes to explore the fundamental workings of the mammalian cell. Genetically tractable, recombinant adenoviruses have become widely used as vectors for gene delivery. Both rational and unbiased methods have been employed to enhance and modify their functional characteristics. Rational approaches to vector optimization are constrained by our incomplete understanding of many viral functions, while unbiased methods are technically limited by the size of the genome and the inherent difficulty of mutagenizing specific genes of interest. This proposal is focused on the development of a novel platform for the creation of customized adenovirus libraries. The critical innovation that underlies this project is a recently developed system for the in vitro assembly of adenovirus genomes from compact modules that can be individually manipulated and then reassembled. In this project, synthetic methods will be employed to generate focal regions of high diversity across the genome of human adenovirus 5, the most widely-employed vector serotype. The resulting DNA sub-libraries will be assembled into complete viral genomes, with each assembly assigned a unique barcode designed to facilitate library characterization and the tracking of individual mutants. The construction and characterization of high-content, focal adenoviral libraries, and their utility, will be demonstrated by a simple screen for mutant viruses that evade recognition by a neutralizing monoclonal antibody. The long term goal of this project is to develop a resource that can be shared and continually developed to meet the evolving needs of scientists across many disciplines.

用于载体优化的合成腺病毒文库