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新冠肺炎has opened many possibilities for different institutions to concoct new vaccine components and to test different approaches to technologies. As the time came for the final phase of Pfizer/BioNTech and Moderna vaccine trials, it showed an astonishing 95% efficacy which gave the people a tighter grip on the string of hope since the pandemic happened. Soon after, fighting the SARS-CoV-2 virus has indeed unlocked the power of mRNA technology.
MRNA技术可能是公众的新手,然而,研究人员在相当长的时间里投注的创新是一项创新。它不仅表现出对SARS-COV-2非常安全和有效的潜力,但也表现出对其他传染病的承诺。
Figure 1. How mRNA Vaccines Work.
Source: National Institutes of Health presentation at Senate hearing (09 September 2020).
In the context of COVID-19, mRNA vaccines instruct cells to create proteins that induce an immune response, creating antibodies that provide protection against future infection.
MRNA疫苗的故事追溯到20世纪90年代初期的一路追溯,当时宾夕法尼亚大学的研究员开始测试MRNA技术作为基因治疗的形式(点击此处了解基因治疗如何工作)。
图2. RNA治疗中的关键发现时间表.
已经有许多基本发现导致建立RNA治疗领域(图2)。从那时起,全年繁殖的无数研究和实验导致了MRNA技术的蓬勃发展。
与传统疫苗不同,通过生长弱化的病毒形式产生数月,可以使用病原体的遗传序列和其他组分以更快的速率生产RNA疫苗。以下是MRNA技术的一些不同应用。
结直肠癌治疗
Research on whether mRNA technology could prevent colorectal cancer from recurring is still in the works. It is known that surgery is the standard treatment for many colorectal cancer patients, however, cancer cells can remain in the body after the tumor is removed. These remaining cancer cells shed DNA into the bloodstream, which is referred to as circulating tumor DNA (ctDNA). Tissue from the tumor is sent off to a specialized lab, where it’s tested to look for genetic mutations that fuel cancer’s growth. Once the mutations have been identified, these are then prioritized by the most common to the least common and an mRNA vaccine is created based on that ranking. The mRNA instructs the patient’s cells to produce protein fragments based on the tumor’s genetic mutations identified during testing. The immune system then searches for other cells with the mutated proteins and clears out any remaining circulating tumor cells.
Figure 3. mRNA Vaccine Design.
治愈自身免疫性疾病
德国研究人员使用MRNA技术在实验性自身免疫性脑脊髓炎(EAE)中将疾病活性降低,例如多发性硬化等疾病。患者经常用免疫抑制药物规定来控制症状,但这些药物可以产生副作用。因此,研究团队创建了一种mRNA疫苗,增加免疫细胞耐受性并降低损伤而不会影响正常的免疫系统功能。
Figure 4. Inducing Tolerance with an Anti-inflammatory mRNA Vaccine.
Gene Therapy
基因治疗是治愈患病细胞的重要治疗策略。然而,常规的基因治疗可能会产生一些风险。由东京大学医学院疾病生物学和整合医学中心的副教授进行的一项研究使用聚合物胶束药物递送系统(DDS)来建立新的MRNA递送系统。使用MRNA进行基因治疗,研究组成功地诱导了嗅觉神经纤维的组织再生,并在具有嗅觉障碍的动物中恢复嗅觉功能。这些朝向使用mRNA作为MRNA的基因疗法的一部分铺平了途径,所述神经系统疾病的许多应用中的基于mRNA的基因疗法。
图5.使用mRNA负载纳米机的基因治疗。
Treatment for Lyme Disease Caused by Tick
The life-threatening Powassan virus has no known prevention or treatment. This is a tick-borne virus that can cause encephalitis in humans, although rare, is circulating in North America and Russia. A new vaccine for the Powassan virus is composed of viral mRNA encapsulated in lipid nanoparticles— this produces subviral particles that build an immune response and elicit protection. The mRNA-based vaccine showed good results against the Powassan virus, it was highly immunogenic and conferred protection against multiple members of the family.
Figure 6. An mRNA Vaccine Protects Mice against Multiple Tick-Transmitted Flavivirus Infections.
ESCO生物安全柜(BSC)积极应用于制造mRNA COVID-19 vaccines in the US. We are looking forward to becoming your partner in providing advanced BSCs and laboratory equipment for your mRNA research. Esco offers fast 1-week lead time for standard units and reasonable lead time for customized lab equipment to suit your specific needs.
References:
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https://www.u-tokyo.ac.jp/focus/en/articles/a_00351.html
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https://www.cancernetwork.com/view/messenger-rna-vaccines-beckoning-of-a-new-era-in-cancer-immunotherapy
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https://www.autoimmuneinstitute.org/articles/mrna-treatment-multiple-sclerosis/
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250668/
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