Ultrasound-Assisted Gene Transfer of Anti-Biofilm Peptides to the Salivary Gland

超声辅助将抗生物膜肽基因转移至唾液腺

基本信息

批准号：
8041732
负责人：
Michael J. Passineau
金额：
$ 11.39万
依托单位：
ALLEGHENY-SINGER RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8041732
关键词：
Address Adjuvant Alternative Therapies Animals Architecture Area Bacteria Biological Factors Bone Tissue Cell membrane Cells Chronic Debridement Dental Dental Hygiene Diet Dose Equilibrium Evaluation Excision Frequencies Gender Gene Delivery Gene Transfer Gene Transfer Techniques Genes Goals Habits Healed Health Host Defense Human In Vitro Individual Inflammation Medical Device Medicine Methods Microbial Biofilms Microbubbles Modeling Mus Non-Human Gene Non-Viral Vector Oral cavity Oral health Pathology Patients Peptides Periodontal Diseases Periodontium Physiologic pulse Physiological Process Production Property Proteins Pseudomonas aeruginosa Public Health Reaction Relative (related person)Reporting Research Rodent Model Saliva Salivary Salivary Glands Streptococcus mutans Structure Techniques Technology Testing Therapeutic Time Tissues Tooth Loss Toothbrushing Ultrasonography Viral Vector antimicrobial base conventional therapy design gene therapy healing immunogenicity microbial microbicide microorganism non-viral gene therapy oral bacteria oral biofilm pathogen pre-clinical research study saliva secretion salivary assay soft tissue therapeutic target therapeutic transgene toothbrush transgene expression

Address Adjuvant Alternative Therapies Animals Architecture Area Bacteria Biological Factors Bone Tissue Cell membrane Cells Chronic Debridement Dental Dental Hygiene Diet Dose Equilibrium Evaluation Excision Frequencies Gender Gene Delivery Gene Transfer Gene Transfer Techniques Genes Goals Habits Healed Health Host Defense Human In Vitro Individual Inflammation Medical Device Medicine Methods Microbial Biofilms Microbubbles Modeling Mus Non-Human Gene Non-Viral Vector Oral cavity Oral health Pathology Patients Peptides Periodontal Diseases Periodontium Physiologic pulse Physiological Process Production Property Proteins Pseudomonas aeruginosa Public Health Reaction Relative (related person)Reporting Research Rodent Model Saliva Salivary Salivary Glands Streptococcus mutans Structure Techniques Technology Testing Therapeutic Time Tissues Tooth Loss Toothbrushing Ultrasonography Viral Vector antimicrobial base conventional therapy design gene therapy healing immunogenicity microbial microbicide microorganism non-viral gene therapy oral bacteria oral biofilm pathogen pre-clinical research study saliva secretion salivary assay soft tissue therapeutic target therapeutic transgene toothbrush transgene expression

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项目摘要

DESCRIPTION (provided by applicant): The present proposal will optimize and apply a method for non-viral gene transfer to the salivary glands. This method utilizes low frequency ultrasound pulses to destroy microbubbles, causing local cavitation and opening transient pores in cell membranes enabling non-viral vectors to enter cells of the salivary gland. This proposed method is derived from existing ultrasound-assisted gene transfer (UAGT) techniques that our group has recently shown is capable of robust, stable, and long-lasting gene transfer to the salivary glands. UAGT has several important advantages over other gene transfer methods, in particular a presumed lack of immunogenicity and therefore the theoretical option to re-dose. Gene transfer to the salivary glands presents the opportunity to achieve endogenous production and salivary secretion of peptide therapeutics. Endogenous production overcomes many of the challenges that have thus far limited the utility of emerging anti-biofilm peptide molecules for targeting individual bad actors in the periodontal flora. Chief among these limitations are manufacturing, stability and delivery of the therapeutics itself, as well as the challenge of achieving a steady-state, sustained concentration of the therapeutic in the saliva. The long-term goal of this research therefore is to lay the pre-clinical groundwork for UAGT to the salivary glands for application in dental medicine. In order to achieve this goal, we will first apply what is already known regarding UAGT to the salivary gland and undertake a careful histopathological evaluation of the effect of this technique on salivary gland architecture and viability. Secondly, we will endeavor an initial proof-of-principle study wherein we will introduce genes with known anti-biofilm activity in model microorganisms (S. mutans and P. aeruginosa) to the salivary glands and assay in vitro the biofilm-inhibiting properties of saliva produced by treated animals. Once this technology has been proven to be reliable, safe and effective in the rodent model, we speculate that it may be an attractive adjuvant or even a primary approach to dealing with destructive microbial pathogens in the periodontium, particularly in vulnerable patients physically incapable of routine oral hygiene. PUBLIC HEALTH RELEVANCE: In this application, we propose to use a non-viral gene therapy approach to address the public health issue of chronic periodontal inflammation and tissue destruction by a subset of oral flora. Specifically, we propose a method of inhibiting biofilm formation, a natural process that is accelerated in the most vulnerable to of dental patients who are unable to maintain routine oral hygiene (i.e. tooth brushing). The immediate application of this technology to public health is to provide a gene therapy-based treatment that may bridge vulnerable patients between episodic periodontal treatments.