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mRNA只是一款新冠疫苗?小看它了

mRNA只是一款新冠疫苗?小看它了

Kat Eschner 2021年05月02日
将攻克许多“无药可医”的疾病

如今,新冠疫情导致诸多行业遭遇严重混乱。但在医药行业里,有个亮点却熠熠生辉:新冠疫苗的研发。目前在研的新冠病毒疫苗包括灭活疫苗、腺病毒载体疫苗和mRNA疫苗,另外还有重组亚单位、合成多肽、DNA等新冠疫苗均在研制中。

“我认为人类正身处疫苗开发的新黄金时代。”比尔及梅琳达·盖茨医学研究所的首席执行官彭妮·希顿说。

各类新冠疫苗中,mRNA疫苗备受关注。

mRNA疫苗属于核酸疫苗。核酸疫苗主要分为DNA型疫苗和RNA型疫苗。DNA型疫苗多应用于肿瘤,而目前在研的新型新冠疫苗多属mRNA型疫苗。

mRNA疫苗的原理是是将RNA在体外进行相关的修饰后传递至机体细胞内表达并产生蛋白抗原,从而导机体产生针对该抗原的免疫应答,进而扩大机体的免疫能力。

专家表示,像辉瑞/BioNTech和Moderna为疫情制造mRNA疫苗一样,利用身体代码治疗疾病的潜力,应用范畴将远远超出当前的疫情。

有些人甚至声称RNA和DNA疗法将改变人类与疾病之间的关系。这意味着将出现新一波技术投入和探索浪潮,对疫苗市场的整体兴趣也会激增。

“人们已经开始认真考虑疫苗业务的经济性,以及如何获得先发优势才能够确保疫苗制造商获得长期的市场主导地位。”SVB Leerink的分析师杰弗里·波格斯说。

前景

为了寻找有效的新冠疫苗,全球各地的开发者尝试了各种疫苗技术。结果是全球各国批准的疫苗各式各样,实现免疫程度也各不相同。

包括现在家喻户晓的辉瑞/BioNTech和Moderna在内,有几家公司转向了从未公开使用但研究已经超过25年,也有一些临床试验支持的技术:合成信使RNA技术。两款mRNA疫苗的免疫效果相当突出,也大大提升了其制造商(对辉瑞的提升更明显)的地位。

当前情况也明确表明,mRNA疫苗可以成为有效的防疫工具。

“通过核酸疫苗,人们发现疫苗能够迅速量产。”通用电气的DNA疫苗相关项目首席研究员约翰·纳尔逊表示,该项目由美国国防部高级研究计划局资助。

跟其他疫苗不一样,RNA和DNA疫苗生产过程涉及装配核酸,以及将脆弱的遗传物质封装以顺利进入细胞。目前的疫苗产品中,封装后会变成极小的脂肪粒。但纳尔逊说,也可以使用其他技术。

这一过程意味着,与其他必须培养有效成分的疫苗相比,mRNA疫苗的制造速度快,调整也相对容易。举例来说,刚开始,mRNA技术主要用于制造个性化癌症药,不过并未大规模应用。

但mRNA在个性化医学领域中确实很有潜力。从季节性流感疫苗之类变化迅速的应用,到迄今无法治疗的病毒,例如寨卡病毒和酶缺乏等之前“无药可医”的疾病,前景非常大。

从长远来看,“多数乃至所有病毒性疾病疫苗都有望应用。”波格斯说。

然而对mRNA疫苗制造商来说,某些特性可能并不值得挑战。

“比如挑战默沙东的宫颈癌疫苗加德西,或葛兰素史克的带状疱疹疫苗欣安立适,挑战非常大,因为标准非常高。”波格斯说。

他预计,mRNA疫苗开发者将开始对经济前景上佳的病症进行临床前研究,但对于已经存在有效疫苗的疾病,即便为高效疫苗投入昂贵冗长的临床试验时,成本效益计算也会有所不同。在某些情况下,加德西的有效性接近100%,而欣安立适的防护几率也比较接近。

传统上,所有疫苗的免疫力都能够超过50%,但对于当前已经有高效防护选择的市场,标准只会更高。

mRNA实验从当前无法治疗的疾病开始可能性比较大,至于已经存在高效疫苗的某些疾病可能永远不会开发。

投资潮

2020年年初,mRNA疫苗已经出现突破,但之前从未量产。

Shore Capital的制药行业分析师亚当·巴克称:“在新冠疫情之前,概念无法证明。”

“大部分RNA疫苗仍然处于临床前动物研究阶段。”希顿说。少数已经进入人体试验阶段的传染病mRNA疫苗都处于早期阶段,其中包括流感和狂犬病疫苗。癌症治疗和疫苗也在试验中。

mRNA应用技术也刚刚出现。将mRNA稳妥送入细胞的方法在2010年代后期才刚由科学家改进,运送mRNA的微小脂肪粒技术上称为脂质纳米颗粒。

“当时我估计要出现获批的RNA疫苗大概还需要5到7年的时间。”希顿说。

不过在新冠疫情中,前所未有的合作环境和政府投资彻底改变了一切,几个月内就通过有效性数据和大规模应用为疫苗提供了概念性验证。

“政府支持帮助制造商在风险中扩大规模,同时获取了第一批有效性数据。”希顿说。

如此一来,当三阶段研究完成,药物准备提交监管部门批准时,企业就已经开始储备剂量。

而政府的大力支持也让Moderna从小型生物技术公司迅速成长为知名制造商,在通用电气向美国国防部高级研究计划局争取的DNA合同中负责RNA部分。

休斯顿卫理公会的RNA治疗学项目医学主任约翰·库克说,学界对其他领域应用RNA研究的兴趣和商业投资也大为增加。

他表示:“该领域发展势头似乎很猛,吸引了不少人员和资金。”

局限性

虽然RNA疫苗和其他疗法似乎前景光明,但也有诸多局限性。“我现在最担心温度稳定性、储存条件和价格。”希顿说,“不过,问题都可以解决。”

技术能够在温度更高的条件下让疫苗保持的稳定。疫苗可以(而且很多人表示应该)获得补贴。

这样可能对全球卫生领域产生巨大影响,进而影响全球底线。

有人提出以市场为基础的战略,例如向疫苗公司加大补贴从而为贫困国家生产疫苗,能够迅速解决问题,不管在财政还是伦理方面都至关重要。

“新冠疫情的一大重要教训是,制药行业提供的巨大益处必须考虑到世界上最贫穷的人们。”最近,两位公共卫生专家在一篇社论中指出。

但即便技术变革和疫苗公平出现进步,希顿还是提醒称,并非所有病毒都像新冠病毒一样容易锁定目标。新冠病毒有标志性的刺突蛋白,进入细胞开始复制的机制相当简单。针对其他病毒时,找出正确靶位以及使用哪种病毒RNA才是巨大挑战。

“突破需要创新。”希顿说。

新冠病毒基因序列发布42天后,Moderna就可以生产出第一款疫苗。

基因序列由上海公共卫生临床中心和公共卫生学院的张永珍领导的科学家团队发布,这一消息本身就代表着科学家之间采取了不同寻常的合作。

去年,学术界、工业界和政府之间在疫苗方面也实现了史无前例的合作。

希顿表示,找到合适的方式继续合作并在此基础上再接再厉,对保持疫苗学黄金时代的发展势头至关重要。

“经验只有实际应用时才能够真正学到。”她说,“除非改变做法。”

mRNA疫苗下一步如何发展?

新冠疫情仍然在持续,它影响了生活的各方各面,现在要估计确切的时间表还比较困难。

巴克预计可以尝试癌症治疗早期探索,特别是现在关于mRNA和癌症的数据非常丰富。疫情开始时,个性化癌症疫苗就已经在试验中,而且与其他治疗方法相比有效性相当高。

但巴克也提醒称,传染病领域能否广泛应用RNA疫苗“最终取决于新冠疫苗的长期数据”。

目前已经应用的两款mRNA疫苗都尚未获得美国食品与药品管理局的全面批准。人们都知道该疫苗对人体不会造成伤害,也可以激发较高的免疫力,但不清楚免疫力能够维持多久。

波格斯说,制药公司虽然面临不确定性,但并未停止临床前研究。至于传染病方面,他预计季节性流感、巨细胞病毒和目前没有疫苗的热带传染病将最先出现成果。

不过“并非每款mRNA疫苗都可以像新冠疫苗一样发生强烈反应。”巴克也警告称。

库克说,直接利用RNA治疗已经开始人体试验,其中包括将未封装的RNA直接注射到相关器官。2019年,Moderna对开腔心脏手术患者心脏再生的治疗进行了一阶段试验。

“使用14号针加上强壮的手臂,就能够到达身体任何部位。”库克说。他指出,现在如果将脂质纳米颗粒注射到血液中,除了身体过滤器肝脏和脾脏,对其他器官都起不了什么作用。

对新冠疫苗来说这点并不重要,因为疫苗注射到手臂肌肉中就可以激发免疫力(这就是为什么注射之后有些人手臂会酸痛)。靶向治疗需要直接到位。情况可能出现变化,他的团队以及其他人都在研究新的更复杂的方法,能够将药物注射到血液中,从而被运送到身体相关部位,不再需要14号针头。

匈牙利科学家卡塔林·卡里科曾经冒着职业风险研发mRNA疗法,她发现辉瑞疫苗如此高效时简直欣喜若狂。

四十年基本上从未获承认的工作中,“我一直想象着可以治疗的各种疾病。”她对《每日电讯报》表示。

现在和不久的将来,在BioNTech工作的卡里科将见证全行业认可她的想法并付诸实施。(财富中文网)

译者:梁宇

审校:夏林

如今,新冠疫情导致诸多行业遭遇严重混乱。但在医药行业里,有个亮点却熠熠生辉:新冠疫苗的研发。目前在研的新冠病毒疫苗包括灭活疫苗、腺病毒载体疫苗和mRNA疫苗,另外还有重组亚单位、合成多肽、DNA等新冠疫苗均在研制中。

“我认为人类正身处疫苗开发的新黄金时代。”比尔及梅琳达·盖茨医学研究所的首席执行官彭妮·希顿说。

各类新冠疫苗中,mRNA疫苗备受关注。

mRNA疫苗属于核酸疫苗。核酸疫苗主要分为DNA型疫苗和RNA型疫苗。DNA型疫苗多应用于肿瘤,而目前在研的新型新冠疫苗多属mRNA型疫苗。

mRNA疫苗的原理是是将RNA在体外进行相关的修饰后传递至机体细胞内表达并产生蛋白抗原,从而导机体产生针对该抗原的免疫应答,进而扩大机体的免疫能力。

专家表示,像辉瑞/BioNTech和Moderna为疫情制造mRNA疫苗一样,利用身体代码治疗疾病的潜力,应用范畴将远远超出当前的疫情。

有些人甚至声称RNA和DNA疗法将改变人类与疾病之间的关系。这意味着将出现新一波技术投入和探索浪潮,对疫苗市场的整体兴趣也会激增。

“人们已经开始认真考虑疫苗业务的经济性,以及如何获得先发优势才能够确保疫苗制造商获得长期的市场主导地位。”SVB Leerink的分析师杰弗里·波格斯说。

前景

为了寻找有效的新冠疫苗,全球各地的开发者尝试了各种疫苗技术。结果是全球各国批准的疫苗各式各样,实现免疫程度也各不相同。

包括现在家喻户晓的辉瑞/BioNTech和Moderna在内,有几家公司转向了从未公开使用但研究已经超过25年,也有一些临床试验支持的技术:合成信使RNA技术。两款mRNA疫苗的免疫效果相当突出,也大大提升了其制造商(对辉瑞的提升更明显)的地位。

当前情况也明确表明,mRNA疫苗可以成为有效的防疫工具。

“通过核酸疫苗,人们发现疫苗能够迅速量产。”通用电气的DNA疫苗相关项目首席研究员约翰·纳尔逊表示,该项目由美国国防部高级研究计划局资助。

跟其他疫苗不一样,RNA和DNA疫苗生产过程涉及装配核酸,以及将脆弱的遗传物质封装以顺利进入细胞。目前的疫苗产品中,封装后会变成极小的脂肪粒。但纳尔逊说,也可以使用其他技术。

这一过程意味着,与其他必须培养有效成分的疫苗相比,mRNA疫苗的制造速度快,调整也相对容易。举例来说,刚开始,mRNA技术主要用于制造个性化癌症药,不过并未大规模应用。

但mRNA在个性化医学领域中确实很有潜力。从季节性流感疫苗之类变化迅速的应用,到迄今无法治疗的病毒,例如寨卡病毒和酶缺乏等之前“无药可医”的疾病,前景非常大。

从长远来看,“多数乃至所有病毒性疾病疫苗都有望应用。”波格斯说。

然而对mRNA疫苗制造商来说,某些特性可能并不值得挑战。

“比如挑战默沙东的宫颈癌疫苗加德西,或葛兰素史克的带状疱疹疫苗欣安立适,挑战非常大,因为标准非常高。”波格斯说。

他预计,mRNA疫苗开发者将开始对经济前景上佳的病症进行临床前研究,但对于已经存在有效疫苗的疾病,即便为高效疫苗投入昂贵冗长的临床试验时,成本效益计算也会有所不同。在某些情况下,加德西的有效性接近100%,而欣安立适的防护几率也比较接近。

传统上,所有疫苗的免疫力都能够超过50%,但对于当前已经有高效防护选择的市场,标准只会更高。

mRNA实验从当前无法治疗的疾病开始可能性比较大,至于已经存在高效疫苗的某些疾病可能永远不会开发。

投资潮

2020年年初,mRNA疫苗已经出现突破,但之前从未量产。

Shore Capital的制药行业分析师亚当·巴克称:“在新冠疫情之前,概念无法证明。”

“大部分RNA疫苗仍然处于临床前动物研究阶段。”希顿说。少数已经进入人体试验阶段的传染病mRNA疫苗都处于早期阶段,其中包括流感和狂犬病疫苗。癌症治疗和疫苗也在试验中。

mRNA应用技术也刚刚出现。将mRNA稳妥送入细胞的方法在2010年代后期才刚由科学家改进,运送mRNA的微小脂肪粒技术上称为脂质纳米颗粒。

“当时我估计要出现获批的RNA疫苗大概还需要5到7年的时间。”希顿说。

不过在新冠疫情中,前所未有的合作环境和政府投资彻底改变了一切,几个月内就通过有效性数据和大规模应用为疫苗提供了概念性验证。

“政府支持帮助制造商在风险中扩大规模,同时获取了第一批有效性数据。”希顿说。

如此一来,当三阶段研究完成,药物准备提交监管部门批准时,企业就已经开始储备剂量。

而政府的大力支持也让Moderna从小型生物技术公司迅速成长为知名制造商,在通用电气向美国国防部高级研究计划局争取的DNA合同中负责RNA部分。

休斯顿卫理公会的RNA治疗学项目医学主任约翰·库克说,学界对其他领域应用RNA研究的兴趣和商业投资也大为增加。

他表示:“该领域发展势头似乎很猛,吸引了不少人员和资金。”

局限性

虽然RNA疫苗和其他疗法似乎前景光明,但也有诸多局限性。“我现在最担心温度稳定性、储存条件和价格。”希顿说,“不过,问题都可以解决。”

技术能够在温度更高的条件下让疫苗保持的稳定。疫苗可以(而且很多人表示应该)获得补贴。

这样可能对全球卫生领域产生巨大影响,进而影响全球底线。

有人提出以市场为基础的战略,例如向疫苗公司加大补贴从而为贫困国家生产疫苗,能够迅速解决问题,不管在财政还是伦理方面都至关重要。

“新冠疫情的一大重要教训是,制药行业提供的巨大益处必须考虑到世界上最贫穷的人们。”最近,两位公共卫生专家在一篇社论中指出。

但即便技术变革和疫苗公平出现进步,希顿还是提醒称,并非所有病毒都像新冠病毒一样容易锁定目标。新冠病毒有标志性的刺突蛋白,进入细胞开始复制的机制相当简单。针对其他病毒时,找出正确靶位以及使用哪种病毒RNA才是巨大挑战。

“突破需要创新。”希顿说。

新冠病毒基因序列发布42天后,Moderna就可以生产出第一款疫苗。

基因序列由上海公共卫生临床中心和公共卫生学院的张永珍领导的科学家团队发布,这一消息本身就代表着科学家之间采取了不同寻常的合作。

去年,学术界、工业界和政府之间在疫苗方面也实现了史无前例的合作。

希顿表示,找到合适的方式继续合作并在此基础上再接再厉,对保持疫苗学黄金时代的发展势头至关重要。

“经验只有实际应用时才能够真正学到。”她说,“除非改变做法。”

mRNA疫苗下一步如何发展?

新冠疫情仍然在持续,它影响了生活的各方各面,现在要估计确切的时间表还比较困难。

巴克预计可以尝试癌症治疗早期探索,特别是现在关于mRNA和癌症的数据非常丰富。疫情开始时,个性化癌症疫苗就已经在试验中,而且与其他治疗方法相比有效性相当高。

但巴克也提醒称,传染病领域能否广泛应用RNA疫苗“最终取决于新冠疫苗的长期数据”。

目前已经应用的两款mRNA疫苗都尚未获得美国食品与药品管理局的全面批准。人们都知道该疫苗对人体不会造成伤害,也可以激发较高的免疫力,但不清楚免疫力能够维持多久。

波格斯说,制药公司虽然面临不确定性,但并未停止临床前研究。至于传染病方面,他预计季节性流感、巨细胞病毒和目前没有疫苗的热带传染病将最先出现成果。

不过“并非每款mRNA疫苗都可以像新冠疫苗一样发生强烈反应。”巴克也警告称。

库克说,直接利用RNA治疗已经开始人体试验,其中包括将未封装的RNA直接注射到相关器官。2019年,Moderna对开腔心脏手术患者心脏再生的治疗进行了一阶段试验。

“使用14号针加上强壮的手臂,就能够到达身体任何部位。”库克说。他指出,现在如果将脂质纳米颗粒注射到血液中,除了身体过滤器肝脏和脾脏,对其他器官都起不了什么作用。

对新冠疫苗来说这点并不重要,因为疫苗注射到手臂肌肉中就可以激发免疫力(这就是为什么注射之后有些人手臂会酸痛)。靶向治疗需要直接到位。情况可能出现变化,他的团队以及其他人都在研究新的更复杂的方法,能够将药物注射到血液中,从而被运送到身体相关部位,不再需要14号针头。

匈牙利科学家卡塔林·卡里科曾经冒着职业风险研发mRNA疗法,她发现辉瑞疫苗如此高效时简直欣喜若狂。

四十年基本上从未获承认的工作中,“我一直想象着可以治疗的各种疾病。”她对《每日电讯报》表示。

现在和不久的将来,在BioNTech工作的卡里科将见证全行业认可她的想法并付诸实施。(财富中文网)

译者:梁宇

审校:夏林

The COVID-19 pandemic has caused profound disruption in many industries, most of it negative. But in the pharmaceutical industry, a bright spot shines.

“I think we are in this new golden age of vaccinology,” says Penny Heaton, chief executive officer of the Bill & Melinda Gates Medical Research Institute.

Experts say the potential of using our body’s code to teach it how to treat illness, as mRNA vaccines from Pfizer/BioNTech and Moderna do for COVID-19, goes far beyond the current pandemic. Some even go so far as to say that RNA and DNA treatments will transform our relationship with disease. What this adds up to is a wave of investment and exploration in the newly proven technology—and a surge of interest in the vaccine market overall.

“People have started to really think about the economics of the vaccine business, and how an early-mover advantage can lead to a dominant long-term market position for a vaccine manufacturer,” says analyst Geoffrey Porges of SVB Leerink.

The prospects

In the search for effective COVID-19 vaccines, developers around the world tried a wide spread of vaccine technologies. The result is a diversity of vaccines approved globally that provoke varying levels of immunity.

A few, including now-household names Pfizer/BioNTech and Moderna, turned to a technology that had never been used in public but had more than 25 years of research and some clinical trials to back it up: synthetically produced messenger RNA. The standout immunity produced by the two successful mRNA vaccines rocketed their makers to (in Pfizer’s case, even greater) prominence.

It also provided stark proof of concept that mRNA vaccines could be a powerful tool against disease. “The promise that a nucleic acid vaccine gives is that it can be made so rapidly,” says John Nelson, General Electric’s lead researcher on a related project for DNA vaccines funded through the Defense Advanced Research Projects Agency (DARPA).

Unlike other vaccine types, producing RNA and DNA vaccines is a matter of assembling nucleic acids and packaging the fragile genetic material in such a way as to protect it until it can make it into a cell. In the case of current vaccines, that package is a tiny particle of fat. But other technologies can be used, says Nelson.

This process means the vaccines are quick to make, compared to other kinds of vaccines that use components that have to be grown, and they can be modified with relative ease. mRNA technology, for instance, was first developed for use in personalized cancer medicine, although it has yet to be implemented at a large scale.

But mRNA has potential beyond personalized medicine. From quick-turnaround applications like seasonal influenza vaccines to as-yet-untreated viruses such as Zika and previously “undruggable” diseases like enzyme deficiencies, its possibilities abound. In the long term, “most or all of the viral disease vaccines are up for grabs,” Porges says.

For mRNA vaccine makers, however, some properties may never be worth challenging. “Breaking in against, for example, Merck’s Gardasil or Glaxo’s Shingrix, that’s got to be more challenging, because the bar is already pretty high,” says Porges.

He expects mRNA vaccine developers to embark on preclinical research on those big-ticket properties, but the cost-benefit calculation for taking even a very effective vaccine into expensive and lengthy clinical trials will be different for conditions that already have effective vaccines. Gardasil has nearly 100% effectiveness in some cases, while Shingrix’s effectiveness is almost that high.

Any vaccine that confers more than 50% immunity is traditionally considered to be effective, but for existing markets with already highly effective options, the bar is much higher. mRNA experimentation is more likely to start with conditions without existing treatments and may never be conducted for some conditions for which highly effective vaccines already exist.

Wave of investment

At the beginning of 2020, mRNA vaccines had promise. But they had never been scaled before.

“Before COVID, there was no proof of concept,” says Adam Barker, a pharmaceutical analyst at Shore Capital.

“Most of the RNA vaccines were still in preclinical animal studies,” says Heaton. The few mRNA vaccines for infectious disease that had reached human trials, including for influenza and rabies, were in early stages. Cancer treatments and vaccines were also in trials.

And the technologies that made mRNA useful were just emerging. A reliable method for getting mRNA into cells—those tiny particles of fat, technically called lipid nanoparticles—had just been optimized by scientists in the late 2010s.

“I would estimate we were probably five to seven years away from having a licensed RNA vaccine in late 2019,” Heaton says.

The unprecedented collaborative environment and government investment prompted by the COVID-19 pandemic entirely changed that reality and provided both proof of concept for the vaccines, in the form of efficacy data and massive scale, in a matter of months.

“The fact that there was government support allowed manufacturers to scale up at risk, and to do that simultaneously while getting that first efficacy data,” Heaton says. That way, when Phase III studies were completed, and the drug was ready to be submitted for regulatory approval, companies were already stockpiling doses.

That kind of support allowed Moderna to rise from a small biotech to a prominent manufacturer who received the RNA portion of the DARPA contract that GE received for DNA. Elsewhere, says John Cooke, medical director of Houston Methodist’s RNA Therapeutics Program, academic interest and business investment in RNA research have spiked.

“There just seems to be a lot more momentum in the field,” he says. “It has attracted personnel and funding.”

Limitations

RNA vaccines and other therapies appear to have a bright future. But there are a number of limitations to their potential. “My biggest qualm right now is the temperature stability, the storage conditions, and the price,” says Heaton. “That said, these are problems that can be solved.”

Technology to keep the vaccines stable at higher temperatures can be developed. Vaccines can (and, many say, should) be subsidized.

Doing so could make a massive difference for global health and thus the global bottom line. Market-based strategies such as deeply subsidizing vaccine companies to produce vaccines for poorer countries have been proposed to quickly move on this issue, which will be an essential one, both financially and morally. “A key lesson of COVID-19 is that the great benefits the pharmaceutical sector has to offer must fully include the world’s poorest people,” two public health experts stated in a recent editorial proposing just this approach.

But even if technological change and advances in vaccine equity happen, Heaton also cautions that not all viruses will be as easy to target as COVID-19. The now-iconic spike protein represents a fairly simple mechanism for the SARS-CoV-2 virus to get into cells and begin replicating. Figuring out the correct parts of the virus to target and which specific viral RNA to use will be a much bigger challenge for many other viruses.

“It’s going to take innovation,” Heaton says.

Moderna was able to produce its first version of its vaccine just 42 days after the release of the SARS-CoV-2 genome’s sequence. That release, by a consortium of scientists headed by Yong-Zhen Zhang of the Shanghai Public Health Clinical Center & School of Public Health, was itself unusual evidence of collaboration between scientists.

Collaboration between academics, industry, and government has been the watchword of the last unprecedented year in vaccinology. Heaton says finding a way to continue that collaboration and build on it will be essential to maintaining the momentum of vaccinology’s golden age.

“A lesson isn’t learned until it’s actually applied,” she says, “until we decide what we are going to do differently.”

What’s next for mRNA vaccines? Since the COVID-19 pandemic is still very much ongoing, interrupting all facets of life, it’s hard to estimate the exact timeline. Barker anticipates that cancer treatments will be an early area of exploration, especially since there’s already so much data about mRNA and cancer. Personalized cancer vaccines were already in trial when the COVID-19 pandemic began, showing a high degree of effectiveness compared to other treatments.

But the widespread use of RNA vaccines for infectious diseases “ultimately depends on what the long-term data on the COVID vaccine is,” Barker cautions. Neither mRNA vaccine currently in use has received full FDA approval yet. Although we know they don’t hurt people and they do produce a high level of immunity, we don’t yet know how long-lasting that immunity is.

This uncertainty hasn’t stopped many drug companies from embarking on at least preclinical research, says Porges. When it comes to infectious diseases, he expects that seasonal influenza, cytomegalovirus, and tropical infectious diseases that don’t currently have a vaccine will be some of the first areas where we see results. But “it won’t be the case that every vaccine based on mRNA will have the same kind of strong response [as the COVID-19 vaccines],” cautions Barker.

Direct RNA treatments, which involve injecting unencapsulated RNA directly into the relevant organs, are already being trialed in humans, says Cooke. In 2019, Moderna’s treatment for heart regeneration in open-heart surgery patients passed through Phase I testing.

“With a 14-gauge needle and a strong arm, you can reach any area in the body,” Cooke says. Right now, lipid nanoparticles, if injected into your bloodstream, don’t do a great job of reaching any organs except the body’s filters, the liver and spleen, he says. That doesn’t matter for the COVID-19 vaccines, since they’re injected into the muscle of your arm and they start provoking immunity from there (that’s why some people get sore arms afterward). Targeted therapies need to be delivered directly. That could change: His team as well as others are working on new, more sophisticated formulations that would allow the drugs to be injected into the bloodstream and carried to the relevant part of the body—no 14-gauge needles involved.

When Katalin Karikó, the Hungarian-born scientist who risked her career to develop mRNA therapy, found out about the Pfizer vaccine’s efficacy, she was overjoyed. During the four decades of largely unacknowledged work, “I imagined all the diseases I could treat,” she told the Telegraph. Now and in the near future, Karikó, who now works for BioNTech, will watch an entire industry take her idea and run with it.

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