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外体的表面功能化,用于向性细胞的siRNA输送和软骨再生
Hao Zhang1, Wenjing Yan2, Jinhui Wang3
1State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, China; EVLiXiR Biotech Inc., Nanjing 210032, Jiangsu, China.
概括
携带siRNA的向外体有效地沉默了细胞中的矩阵金属酶13 (MMP13),通过减少软骨退化,为骨关节炎 (OA) 提供了一个有前途的新疗法.
科学领域:
- 生物医学工程 生物医学工程
- 软骨生物学 软骨生物学
- 药物输送系统 药物输送系统
背景情况:
- 骨关节炎 (OA) 是一种常见的退行性软骨疾病,没有有效的治疗方法.
- 冠状细胞功能障碍,包括矩阵金属酶13 (MMP13) 的过度表达,导致OA的软骨退化.
- 有效地将治疗药物输送到软骨内的软骨细胞仍然是一个重大挑战.
研究的目的:
- 开发一种针对性外体基传递系统,将siRNA传递给软体细胞.
- 在骨关节炎大鼠模型中研究MMP13抑制外体的疗效.
主要方法:
- 工程外体与软骨亲和 (CAP) 用于状细胞向 (CAP-Exo).
- 对MMP13 (siMMP13) 用siRNA加载CAP-Exo,以创建CAP-Exo/siMMP13.3,从而产生一个CAP-Exo/siMMP13.
- 在前十字带截切 (ACLT) 诱导的OA小鼠模型中,CAP-Exo/siMMP13的关节内给药.
主要成果:
- 在OA大鼠的软骨中,CAP-Exo/siMMP13成功降低了MMP13水平.
- 治疗增加了原蛋白COL2A1和蛋白质甘氨酸水平,表明软骨修复.
- 蛋白质组分析证实IL-1β治疗的红细胞中蛋白质配置的恢复.
结论:
- 一种简单的外体工程方法使得有针对性的siRNA传递到体细胞.
- 使用CAP-Exo/siMMP13对状细胞特异的MMP13静音减轻了OA中的软骨退化.
- 这种方法有可能开发新的OA治疗方法.
相关概念视频
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
02:57piRNA - Piwi-interacting RNAs
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
02:30Small interfering RNAs (siRNA)
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...