PRODUCE/TEST ADENOVIRUS VECTORS FOR CLINICAL USE

生产/测试用于临床用途的腺病毒载体

• 批准号: 6293106
• 负责人: JEFFREY M OSTROVE
• 金额: --
• 依托单位: MICROBIOLOGICAL ASSOCIATES, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2000-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6293106
• 关键词: Adenoviridae; drug design /synthesis /production; drug screening /evaluation; gene expression; gene targeting; link protein; recombinant virus; salivary glands; transfection; transfection /expression vector

Salivary hypofunction that follows the loss of acinar cells is debilitating for patients and tends to be progressive and irreversible. This type of hypofunction is typical of patients who have had therapeutic radiation involving the glands, or patients with Sjogren's syndrome. One approach to this clinical problem is to increase the water-secreting capacity of the cells that remain in diseased glands. Candidate proteins for this function have been identified (aquaporins), and preclinical data suggest that the aquaporins may be useful in improving the function of radiated salivary glands. On the other hand, normal salivery glands may secrete therapeutic proteins for disorders of the oral and pharyngeal tissues. For example, antimicrobial proteins might be secreted in the saliva for the treatment of mucosal infections. In either case, these strategies depend on the efficient transfer of the exogenous gene to the salivary glands. For this purpose, adenovirus-based vectors are the best available candidates for salivary gland gene transfer. The purpose of this project is to produce clinical grade adenovirus vectors for use in the salivary glands, as part of Phase I clinical trials. The production of adenovirus vectors for clinical applications requires specialized knowledge, considerable skill, and dedicated facilities.

腺泡细胞丧失后的唾液功能减退 使患者虚弱，并倾向于进行性和 不可逆转。这种类型的功能减退是典型的 曾接受过累及腺体的放射治疗，或患者 患有干燥综合征。解决这个临床问题的一种方法是 增加残留在体内的细胞的分泌水分能力 有病的腺体。具有这一功能的候选蛋白质是 已鉴定的(水通道蛋白)和临床前数据表明 水通道蛋白可能有助于改善辐射损伤的功能。 唾液腺。另一方面，正常的唾液腺可能 分泌治疗口腔和口腔疾病的治疗蛋白 咽部组织。例如，抗菌蛋白质可能是 分泌在唾液中，用于治疗粘膜感染。在……里面 无论是哪种情况，这些策略都依赖于 外源基因进入唾液腺。为此， 以腺病毒为基础的载体是最好的候选 唾液腺基因转移。这个项目的目的是 生产用于唾液的临床级腺病毒载体 腺体，作为I期临床试验的一部分。产品的生产 临床应用的腺病毒载体需要专门的 知识，相当的技能，和专门的设施。