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Maximizing small RNA delivery with signaling pepitdes

通过信号肽最大化小 RNA 递送

基本信息

批准号：
9145216
负责人：
Juliane Nguyen
金额：
$ 23.59万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-16 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9145216
关键词：
Adverse effects Bacteriophages Biocompatible Materials Biological Assay Biological Availability Biomedical Engineering Carrier Proteins Cell Separation Cells Cellular biology Charge Clinical Code Coupled Cytoplasm Data Development Dose Drug Delivery Systems Formulation Future Gene Silencing Goals Health Immune Lead Libraries Measures Mediating MicroRNAs Molecular Multivesicular Body Nucleic Acids Particle Size Particulate Peptide Signal Sequences Peptides Process Property Protein Engineering Proteins RNA RNA Recognition Motif RNA-Induced Silencing Complex Research Safety Signal Transduction Site Small Interfering RNA Small RNA Sorting - Cell Movement Staging Surface Techniques Testing Therapeutic Treatment Efficacy Virus base cancer cell cell type design health application human disease improved in vivo interdisciplinary approach nanocarrier nanotherapeutic novel protein aminoacid sequence receptor screening trafficking

项目摘要

DESCRIPTION (provided by applicant): The objective of this mechanism-based research is to devise safe and efficient protein particulate nanocarriers (PPC) for small RNA delivery. To accomplish this, we plan to exploit the intracellular trafficking machinery to direct the delivery f small RNAs to their site of action while maximizing small RNA delivery. Small RNAs are used in a range of health applications. However, their potential has yet to be fully realized. This is largely due to inefficient delivery: only 1-2% of small RNAs reach the RNA-induced silencing complex (RISC): the site of action using conventional techniques. Small RNA delivery is a multistep process in which inefficiencies at any stage can compromise the efficacy of gene silencing. In particular, the intracellular fate of synthetic carriers is not well understood and tus poorly controlled. Recent studies indicate that active RISCs are functionally and physically coupled to MVBs and are not free in the cytoplasm as previously thought. Thus, we hypothesize that the effect of small RNA delivery can be significantly increased by actively targeting MVBs. We propose the design of PPCs containing signaling moieties that are recognized by the cell sorting machinery and that serve as "molecular zip codes" for the directed transport of small RNAs to the RISC. This could ultimately lead to enhanced gene silencing. This strategy could improve RNA-based therapy by allowing for the administration of lower doses of therapeutics, thereby reducing side effects and improving safety profiles.