Bladder Pain Gene Therapy with Pro-opiomelanocortin cDNA
使用阿黑皮质素原 cDNA 进行膀胱疼痛基因治疗
基本信息
- 批准号:6803574
- 负责人:
- 金额:$ 11.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-09-30 至 2006-08-31
- 项目状态:已结题
- 来源:
- 关键词:TaiwanUnited Statesacetatesbiotechnologycomplementary DNAcyclophosphamidedisease /disorder modelendorphinsfemalegene delivery systemgene expressiongene therapyhuman genetic material tagimmunocytochemistryinternational cooperationinterstitial cystitislaboratory ratnonhuman therapy evaluationpainproopiomelanocortinprotein localizationtransfection
项目摘要
DESCRIPTION (provided by applicant): Interstitial cystitis (IC) is a bladder hypersensitivity disease associated with bladder pain, which has been a major challenge to understand and treat. We hypothesize that targeted and localized expression of endogenous opioid peptide in the bladder could be useful for the treatment of bladder pain. Pro-opiomelanocortin (POMC) is one of such precursor molecules for an opioid peptide, beta-endorphin. In this R21 grant proposal, using a gene-gun method for the transfer of POMC cDNA in vivo that we have recently developed, and investigated its efficacy and safety on acetic acid and cyclophosphamid-induced bladder hyperactivity in the rats. Human POMC cDNA was cloned into a modified pCMV plasmid. We will deliver the cDNA into the bladder wall of adult female rats by direct injection or gene-gun. We will evaluate short and long-term effects of this form of therapy with acute and chronic bladder hyperactivity models using acetic acid and cyclophosphamid. Physiological testing with cystometrograms and immunohistochemical testing will be used to detect endorphin after POMC cDNA transfer. We believe that POMC gene can be transferred in the bladder using gene-gun and that increased expression of endorphin in the bladder can suppress nociceptive responses induced by bladder irritation. Thus POMC gene-gun, delivered through the working port of a cystoscope, may be useful for the treatment of IC and other types of visceral pain. The long-term objective of this R21 project is to develop convincing data to justify a RO1 submission within the two years time frame of the project. Moreover, we want to establish a safe and effective concept of nonviral gene therapy for the treatment of the painful bladder syndromes. This research project is important to provide a solid basis for potential future clinical application.
描述(由申请人提供):间质性膀胱炎(IC)是一种与膀胱疼痛相关的膀胱超敏反应性疾病,这一直是理解和治疗的主要挑战。我们假设内源性阿片肽在膀胱中的靶向和局部表达可能有助于治疗膀胱疼痛。前阿黑皮素(POMC)是阿片肽β-内啡肽的前体分子之一。在这项R21资助计划中,使用我们最近开发的基因枪方法在体内转移POMC cDNA,并研究其对乙酸和环磷酰胺诱导的大鼠膀胱过度活动的有效性和安全性。将人POMC cDNA克隆到经修饰的pCMV质粒中。我们将通过直接注射或基因枪将cDNA导入成年雌性大鼠膀胱壁。我们将评估这种形式的治疗的短期和长期影响与急性和慢性膀胱功能亢进模型使用乙酸和环磷酰胺。在POMC cDNA转移后,将使用膀胱测量图和免疫组织化学测试的生理测试来检测内啡肽。我们认为,POMC基因可以通过基因枪转移到膀胱内,增加膀胱内内啡肽的表达可以抑制膀胱刺激引起的伤害性反应。因此,POMC基因枪,通过膀胱镜的工作端口提供,可能是有用的IC和其他类型的内脏疼痛的治疗。该R21项目的长期目标是在项目的两年内开发令人信服的数据,以证明提交的RO 1。同时,我们希望建立一个安全有效的非病毒基因治疗膀胱疼痛综合征的概念。该研究项目对于为未来潜在的临床应用提供坚实的基础非常重要。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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NAOKI YOSHIMURA其他文献
NAOKI YOSHIMURA的其他文献
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{{ truncateString('NAOKI YOSHIMURA', 18)}}的其他基金
Afferent and urothelial plasticity underlying bladder sensitization in prostatic inflammation
前列腺炎症中膀胱敏感的传入和尿路上皮可塑性
- 批准号:
10002343 - 财政年份:2016
- 资助金额:
$ 11.7万 - 项目类别:
Neurophysiology and Biomechanics of Urethra in SUI
SUI 尿道的神经生理学和生物力学
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6761522 - 财政年份:2004
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$ 11.7万 - 项目类别:
Neurophysiology and Biomechanics of Urethra in SUI
SUI 尿道的神经生理学和生物力学
- 批准号:
6868207 - 财政年份:2004
- 资助金额:
$ 11.7万 - 项目类别:
Neurophysiology and Biomechanics of Urethra in Stress Urinary Incontinence
压力性尿失禁尿道的神经生理学和生物力学
- 批准号:
7395042 - 财政年份:2004
- 资助金额:
$ 11.7万 - 项目类别:
Neurophysiology and Biomechanics of Urethra in Stress Urinary Incontinence
压力性尿失禁尿道的神经生理学和生物力学
- 批准号:
7228532 - 财政年份:2004
- 资助金额:
$ 11.7万 - 项目类别:
Neurophysiology and Biomechanics of Urethra in SUI
SUI 尿道的神经生理学和生物力学
- 批准号:
7054143 - 财政年份:2004
- 资助金额:
$ 11.7万 - 项目类别:
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