Drug and Gene Delivery to the Back of the Eye: From Bench to Bedside

描述（由申请人提供）：视网膜疾病包括年龄相关性黄斑变性、糖尿病视网膜病变、青光眼和遗传性视网膜世代是世界上失明的主要原因。随着预期寿命的增加和糖尿病的流行，视网膜疾病的社会经济负担预计将是巨大的。视网膜疾病治疗发展的速度限制步骤包括确定新的治疗药物以及将这些药物输送到眼后组织的新方法。随着siRNA、miRNA和基因疗法等新型治疗药物的发现，开发新型递送系统的需求也在不断升级。由于缺乏适当的递送系统，一些核酸疗法可能会失败，这些系统可以a)保护治疗剂不被核酸酶降解，b)允许增强细胞进入，c)最小化脱靶效应，以及d)在治疗慢性视网膜疾病时提供延长递送。即使有成功的蛋白质治疗药物，如雷尼单抗，几年来频繁注射可能对视网膜健康有害。这一限制可以通过开发蛋白质药物的长期给药方法来克服。对于小分子药物，无创的眼后给药尚未成为临床现实。此外，即使通过侵入性方法，维持小水溶性分子向眼睛后部的输送也是一个主要挑战。为了加快新的小分子、蛋白质和核酸治疗剂从实验室到临床的转化，本次会议的目的是在包括学术界、工业界和监管机构代表在内的不同参与者群体之间分享基于药物开发原则的前沿科学。预计听众将来自不同的个人群体，包括那些代表少数民族和传统上在科学事业中代表性不足的社区的人。为期两天的会议将包括口头和海报展示。为本次会议提供的资金支持将有助于招募顶尖科学家和参与者。此外，还将提供注册费减免和旅行奖励，以鼓励少数民族和代表性不足的社区参与。根据会议上的介绍和讨论，将在会议结束后3个月内撰写白皮书，并及时提交在眼科杂志上发表。

DESCRIPTION (provided by applicant): Retinal disorders including age related macular degeneration, diabetic retinopathy, glaucoma and inherited retinal generations are major causes of blindness in the world. With an increase in life expectancy and growing diabetes epidemic, the socioeconomic burden of retinal disorders is expected to enormous. Rate limiting steps in the development of treatments for retinal disorders include identification of new therapeutic agents as well as new approaches to deliver these agents to the tissues of the back of the eye. With the identification of new therapeutic agents such as siRNA, miRNA, and gene therapies, the need for the development of novel delivery systems also escalates. Several nucleic acid therapies may fail due to the lack of availability of appropriate delivery systems that can a) protect the therapeutic agent from degradation by nucleases, b) allow enhanced cellular entry, c) minimize off-target effects, and d) offer prolonged delivery in treating chronic retinal disorders. Even with successful protein therapeutic agents such as ranibizumab, frequent injections over several years might be detrimental to retinal health. This limitation can potentially be overcome through the development of long term delivery approaches for protein drugs. For small molecule drugs, noninvasive delivery to the back of the eye has yet to become a clinical reality. Further, sustaining the delivery of small water soluble molecules to the back of the eye even by invasive approaches is a major challenge. In order to expedite the translation of new small molecule, protein, and nucleic acid therapeutic agents from the bench to the bedside, the purpose of this conference is to share cutting edge science based on drug product development principles among a diverse group of participants, including representatives from academia, industry, and regulatory agencies. The audience is expected to be drawn from a diverse group of individuals including those representing minorities and traditionally underrepresented communities in science careers. The two day conference will include oral as well as poster presentations. Financial support provided for this conference will be helpful in recruiting top scientists as well as participants. In addition, registration fee waivers and travel awards will be provided in order to encourage participation by minorities and underrepresented communities. Based on the presentations and discussions at the conference, a white paper will be prepared within 3 months after the conference and submitted for publication in a timely manner in an ophthalmology journal. PUBLIC HEALTH RELEVANCE: Blinding retinal disorders have a major socioeconomic impact. A rate limiting step in advancing new therapeutic agents from bench to bedside is the delivery to the affected target cells. Each class of therapeutic agents poses unique problems in developing clinically usable delivery systems. Most recently, siRNA based therapies have met with limited success potentially due to their off-target effects on the cell surface. Such therapeutic agents should enter the cell, while avoiding interactions with some cell surface receptors. In order to expedite the clinical translation of new therapeutic agents, the purpose of this conference is to present cutting edge science based approaches for developing new drug products for treating back of the eye diseases.