关于开发一种新型结构化微混合器和评估纳米粒子产品作为mRNA传递载体的全周期研究
Gi-Su Na1, Jeong-Un Joo1, Joo Young Lee2
1Center for Intelligent Microprocess of Pharmaceutical Synthesis, Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
概括
一个新的3D打印的双混合器 (DVM) 提高了纳米粒子生产的统一性和一致性. 这种微流体设备克服了混合效率低下和堵塞,使得可扩展的,高质量的纳米粒子合成疗法.
科学领域:
- 纳米技术纳米技术
- 生物医学工程 生物医学工程
- 材料科学 材料科学 材料科学
背景情况:
- 精确控制纳米粒子大小和均性对于有效的基于纳米粒子的疗法至关重要.
- 微流体合成提供了可靠性,但与混合效率和通道堵塞作斗争,阻碍了质量控制和可扩展性.
- 现有的方法在实现治疗应用所需的均性方面面临挑战.
研究的目的:
- 开发一种用于增强纳米粒子合成的新型微流体混合器.
- 解决当前微流体设备的局限性,特别是混合效率和运行堵塞.
- 为了生产高度统一的纳米粒子用于治疗应用,并改进了质量控制.
主要方法:
- 开发一个3D打印的双混合器 (DVM) 与半球波形微观结构.
- 整合迪恩,以创建强化的二次流,以便快速混合.
- 脂质,脂质体和聚合物纳米颗粒的合成和表征,包括载有mRNA的脂质纳米颗粒.
主要成果:
- 该DVM证明了快速混合并产生高度均的纳米粒子 (50-130nm),其多分散度指数 (PDI) 低于0.15.
- SARS-CoV-2 Spike mRNA装载的脂质纳米颗粒在体外和体内表达的蛋白质表达与商业混合器相比较.
- 在半天的运行过程中,DVM确保了在没有内部堵塞的情况下的一致生产,从而促进了质量控制和可扩展性.
结论:
- 新的DVM有效地克服了纳米粒子合成的微流体混合限制.
- 这项技术使得可扩展,无堵塞的生产高度统一的纳米粒子用于治疗应用.
- 在纳米颗粒制造中,DVM提供了一个有前途的解决方案,用于在纳米颗粒制造中进行一致的质量控制.
相关概念视频
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
02:24Regulation of Expression Occurs at Multiple Steps
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
02:22Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
02:51mRNA Stability and Gene Expression
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
01:25Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...