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阴道内 siRNA 传递领域的进展。

Advancements in the field of intravaginal siRNA delivery.

机构信息

Faculty of Pharmacy, University of Manitoba, 750 McDermot Ave, Winnipeg, Manitoba, Canada.

出版信息

J Control Release. 2013 Apr 10;167(1):29-39. doi: 10.1016/j.jconrel.2012.12.023. Epub 2013 Jan 5.

DOI:10.1016/j.jconrel.2012.12.023
PMID:23298612
Abstract

The vaginal tract is a suitable site for the administration of both local and systemic acting drugs. There are numerous vaginal products on the market such as those approved for contraception, treatment of yeast infection, hormonal replacement therapy, and feminine hygiene. Despite the potential in drug delivery, the vagina is a complex and dynamic organ that requires greater understanding. The recent discovery that injections of double stranded RNA (dsRNA) in Caenorhabditis elegans (C. elegans) results in potent gene specific silencing, was a major scientific revolution. This phenomenon known as RNA interference (RNAi), is believed to protect host genome against invasion by mobile genetic elements such as transposons and viruses. Gene silencing or RNAi has opened new potential opportunities to study the function of a gene in an organism. Furthermore, its therapeutic potential is being investigated in the field of sexually transmitted infections such as human immunodeficiency virus (HIV) and other diseases such as age-related macular degeneration (AMD), diabetes, hypercholesterolemia, respiratory disease, and cancer. This review will focus on the therapeutic potential of siRNA for the treatment and/or prevention of infectious diseases such as HIV, HPV, and HSV within the vaginal tract. Specifically, formulation design parameters to improve siRNA stability and therapeutic efficacy in the vaginal tract will be discussed along with challenges, advancements, and future directions of the field.

摘要

阴道是局部和全身作用药物给药的合适部位。市场上有许多阴道产品,例如那些用于避孕、治疗酵母感染、激素替代疗法和女性卫生的产品。尽管在药物输送方面有很大的潜力,但阴道是一个复杂而动态的器官,需要更多的了解。最近发现,在秀丽隐杆线虫(C. elegans)中注射双链 RNA(dsRNA)会导致强烈的基因特异性沉默,这是一项重大的科学革命。这种现象称为 RNA 干扰(RNAi),据信可以保护宿主基因组免受转座子和病毒等移动遗传元件的入侵。基因沉默或 RNAi 为研究生物体中基因的功能开辟了新的潜在机会。此外,其治疗潜力正在研究中,例如在性传播感染(如人类免疫缺陷病毒(HIV))和其他疾病(如年龄相关性黄斑变性(AMD)、糖尿病、高胆固醇血症、呼吸道疾病和癌症)领域。本综述将重点介绍 siRNA 治疗和/或预防阴道内 HIV、HPV 和 HSV 等传染病的治疗潜力。具体来说,将讨论改善 siRNA 在阴道内稳定性和治疗效果的配方设计参数,以及该领域的挑战、进展和未来方向。

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