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Partillion Bioscience寻求通过基于NGS的分泌蛋白检测进行扩展

Partillion Bioscience Seeks Expansion With NGSased, Secreted Protein Assays

GenomeWeb 等信源发布 2024-09-05 15:27

可切换为仅中文


NEW YORK – Partillion Bioscience, a spinout from the University of California, Los Angeles, is looking to expand its customer base with the launch of an early-access program for its new sequencing-based assays for detecting proteins secreted by cells.

纽约——加利福尼亚大学洛杉矶分校的分支机构Partillion Bioscience正在寻求扩大其客户基础,推出一项早期访问计划,用于检测细胞分泌蛋白质的基于测序的新检测方法。

The firm's new multicell assays build upon its nanovial technology, developed in the lab of UCLA's Dino Di Carlo. Partillion launched with the ability to isolate single cells and analyze secreted proteins, captured by the droplet-emulsified, bowl-like glass particles. Now, bigger particles allow researchers to perform studies 'where the precise colocalization of cells is essential for studying complex cell-to-cell interactions or screening for therapeutic molecules released by one cell that act on another,' said Joe de Rutte, CEO and cofounder of Partillion.

该公司新的多细胞检测技术建立在其纳米瓶技术的基础上,该技术是在加州大学洛杉矶分校的迪诺·迪卡罗实验室开发的。Partillion能够分离单个细胞并分析分泌的蛋白质,这些蛋白质被液滴乳化的碗状玻璃颗粒捕获。Partillion首席执行官兼联合创始人乔·德拉特(JoeDeRutte)说,现在,较大的颗粒使研究人员能够进行研究,“细胞的精确共定位对于研究复杂的细胞间相互作用或筛选一个细胞释放的作用于另一个细胞的治疗分子至关重要。”。

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'By enabling these complex screens, we're enabling scientists to scale studies of how cells interact with other cells, whether it's better understanding tumors in the context of immune cells in their microenvironment, [analyzing] host-pathogen interactions, or developing next-generation therapies.'

“通过启用这些复杂的筛选,我们使科学家能够规模化研究细胞如何与其他细胞相互作用,无论是在免疫细胞的微环境中更好地理解肿瘤,[分析]宿主-病原体的相互作用,还是开发下一代疗法。”

A major application of the firm's technology is antibody discovery and the multicell nanovials will enable researchers to look at how secreted proteins affect neighboring cells. Importantly, the firm's kits allow this without the use of specialized instrumentation, de Rutte said.

该公司技术的一个主要应用是抗体发现,多细胞纳米小瓶将使研究人员能够研究分泌的蛋白质如何影响邻近细胞。de Rutte说,重要的是,该公司的套件不需要使用专门的仪器就可以实现这一点。

Company researchers posted a preprint to BioRxiv in mid-August in collaboration with partner Alloy Therapeutics, presenting a method for discovering monoclonal antibodies from plasma B cells. Proof-of-concept experiments paired antibody-secreting cells with cells expressing a target protein. Single-cell sequencing of the isolated antibody-producing cells yielded the heavy- and light-chain sequences.

公司研究人员于8月中旬与partner Alloy Therapeutics合作,向BioRxiv发布了一份预印本,介绍了一种从血浆B细胞中发现单克隆抗体的方法。概念验证实验将抗体分泌细胞与表达靶蛋白的细胞配对。分离的产生抗体的细胞的单细胞测序产生重链和轻链序列。

An antibody discovery campaign targeting  the immune checkpoint protein PD-1 yielded molecules with similar binding affinities to the therapies pembrolizumab and nivolumab, the authors wrote..

作者写道,针对免疫检查点蛋白PD-1的抗体发现活动产生了与pembrolizumab和nivolumab疗法具有相似结合亲和力的分子。。

'Secreted proteins represent something like 20 percent of the proteome and we don't really understand a lot of the factors that lead to their regulation of other cells,' said Richard James, an immunology researcher at the University of Washington and a Partillion collaborator. His lab is one of several that are using Partillion's technology to investigate this area of biology.

华盛顿大学(University of Washington)免疫学研究员、Partillion合作者理查德·詹姆斯(Richard James)说:“分泌的蛋白质约占蛋白质组的20%,我们并不真正了解导致其调节其他细胞的许多因素。”。他的实验室是使用Partillion技术研究这一生物学领域的几个实验室之一。

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De Rutte founded Partillion in the spring of 2020 at the end of his doctoral studies under Dino Di Carlo, a bioengineering professor and the firm's other cofounder. Di Carlo's lab specializes in microfluidics and has also helped develop a handheld magnet-driven molecular diagnostics device. It has spun out other startups, including Cytovale, a diagnostics company commercializing a sepsis test.

2020年春天,在生物工程教授迪诺·迪卡罗(DinoDiCarlo)和该公司的另一位联合创始人的带领下,德拉特(DeRutte)在博士研究结束后成立了Partillion。迪卡罗的实验室专门研究微流体,并帮助开发了一种手持式磁铁驱动的分子诊断设备。。

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The lab was looking for a way to do microfluidics in small reaction chambers to isolate cells 'but in a way that lets people use the tools they have in their lab,' de Rutte said. The biotinylated nanovials were a solution that helped them not just isolate cells but also capture the information around them.

德鲁特说,实验室正在寻找一种在小型反应室中进行微流体分离细胞的方法,但这种方法可以让人们使用实验室中的工具。生物素化的纳米小瓶是一种解决方案,不仅可以帮助他们分离细胞,还可以捕获细胞周围的信息。

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At first, they designed them to be compatible with flow cytometers, of which there are thousands in labs around the world. The instruments could capture certain cells and allow researchers to perform single-cell assays on them. 'We did a lot around proteins being secreted by cells. Not just cell surface proteins, but cytokines and antibodies,' de Rutte said.

起初,他们将其设计为与流式细胞仪兼容,世界各地的实验室中有数千台流式细胞仪。这些仪器可以捕获某些细胞,并允许研究人员对其进行单细胞检测。”我们围绕细胞分泌的蛋白质做了很多工作。德鲁特说,不仅是细胞表面蛋白,还有细胞因子和抗体。

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Their proof of concept was in cell line development. After talking to scientists in that field, de Rutte said he realized they were hesitant to adopt complex new instrumentation, such as the Berkeley Lights Beacon, which was launched in 2016. (That firm went public in 2020, but struggled to place instruments and was ultimately acquired by Bruker a year ago for $108 million.).

他们的概念证明是在细胞系开发中。在与该领域的科学家交谈后,德拉特说,他意识到他们对采用复杂的新仪器犹豫不决,例如2016年推出的伯克利灯塔。(该公司于2020年上市,但很难放置仪器,最终于一年前以1.08亿美元被布鲁克收购)。

At first, the technology was used mostly for screening cells, but the 'aha!' moment came with being able to link functional information with a cell's gene expression. 'There are a lot of applications where you want to isolate cells but keep them alive to do downstream sequencing,' de Rutte said. Partillion also found that it could simply load its nanovials into a 10x Genomics Chromium single-cell instrument to get gene expression data..

起初,该技术主要用于筛选细胞,但“啊哈!”这一刻到来了,人们能够将功能信息与细胞的基因表达联系起来。”DeRutte说,有很多应用程序需要分离细胞,但要让它们保持活力才能进行下游测序。Partillion还发现,它可以简单地将其纳米小瓶装入10倍基因组学铬单细胞仪器中,以获得基因表达数据。。

Partillion has now raised 'a few hundred thousand dollars' in pre-seed financing, followed by a December 2022 seed round of approximately $5 million, led by ND Capital and joined by Vertical Venture Partners and Paladin Capital. The company has also obtained National Institutes of Health Small Business Innovation Research Grants totaling approximately $3 million.

Partillion现在已经在种子前融资中筹集了“几十万美元”,随后在2022年12月进行了一轮约500万美元的种子融资,由ND Capital牵头,垂直风险合作伙伴和Paladin Capital加入。该公司还获得了美国国立卫生研究院小企业创新研究资助,总计约300万美元。

'We've been lean and efficient,' de Rutte said, adding that he may consider looking at raising funds sometime next year. The company has 15 full-time employees and has licensed IP from UCLA and developed its own IP..

德拉特说,我们一直精干高效,并补充说,他可能会考虑明年某个时候筹集资金。该公司有15名全职员工,拥有加州大学洛杉矶分校的知识产权许可证,并开发了自己的知识产权。。

Several Di Carlo lab collaborators have published papers using the nanovial technology, including James, who is trying to turn antibody-secreting cells into factories for other proteins. Proof-of-concept studies have shown that 'some of them have the features we want, and others don't,' he said. 'We really wanted a way to understand the basis of that heterogeneity.'.

迪卡罗实验室的几位合作者发表了使用纳米瓶技术的论文,其中包括詹姆斯,他正试图将抗体分泌细胞转化为其他蛋白质的工厂。他说,概念验证研究表明,“其中一些具有我们想要的功能,而另一些则没有。”我们真的想找到一种方法来理解这种异质性的基础。”。

The lab had engaged with Berkeley Lights about buying a Beacon, 'but I just didn't want to spend a million dollars on their piece of equipment that didn't do everything we wanted to do,' James said. 'Partillion's technology is really flexible.'

詹姆斯说,实验室曾与伯克利灯光公司(BerkeleyLights)就购买灯塔一事进行过接触,“但我不想在他们的设备上花费100万美元,因为这些设备并没有做到我们想做的一切。”Partillion的技术非常灵活。”

The nanoparticles are available for sale on their own and can work with commercially available antibodies and flow cytometers. Partillion offers them in two sizes: a 35-micron outer diameter for single cells and 50 microns with larger cavities for the multi-cell assays or larger cells.

纳米颗粒可自行销售,可以与市售抗体和流式细胞仪一起使用。Partillion为它们提供了两种尺寸:单个细胞的外径为35微米,多细胞检测或较大细胞的腔径为50微米。

Tubes of Nanovials start at $1,000, which contain enough to process 200,000-400,000 cells. Larger kit formats are available and come a bulk discount. Partillion also has ready-to-use kits for certain applications, such as antibody discovery. The kits include Nanovials, validated antibodies for certain cell targets, detection antibodies for secreted targets and other reagents needed for the workflow, 'typically in the $2,000 to $3,000 range,' de Rutte said..

纳米小瓶管的起价为1000美元,其中含有足够处理200000-400000个细胞。较大的套件格式可用,并提供批量折扣。Partillion还为某些应用提供了现成的试剂盒,例如抗体发现。DeRutte说,这些试剂盒包括纳米小瓶、针对某些细胞靶标的经过验证的抗体、针对分泌靶标的检测抗体以及工作流程所需的其他试剂,“通常在2000美元至3000美元的范围内”。。

The firm's customer base 'skews towards pharma,' he said, with only about 25 percent of customers in academic labs. For the new early-access program, Partillion is looking to work with between five and 10 labs, who will receive free reagents and antibodies for particular validated workflows. The firm has already begun with certain early access customers; it is primarily focused on advancing antibody discovery applications.

他说,该公司的客户群“倾向于制药”,只有约25%的客户在学术实验室。对于新的早期访问计划,Partillion希望与5到10个实验室合作,这些实验室将为特定的经过验证的工作流程提供免费的试剂和抗体。该公司已经开始与某些早期访问客户合作;它主要专注于推进抗体发现应用。

The new multicell kits solve some problems of antibody discovery against certain targets that maintain their physiological structure only in their native cellular context, such as G-protein coupled receptors and immune checkpoint proteins, de Rutte said, adding that chimeric antigen receptor T cell screening and cytokine profiling of immune cells are other areas the company is exploring for future commercial offerings..

de Rutte说,新的多细胞试剂盒解决了针对某些仅在其天然细胞环境中维持其生理结构的靶标的抗体发现的一些问题,例如G蛋白偶联受体和免疫检查点蛋白,并补充说,嵌合抗原受体T细胞筛选和免疫细胞的细胞因子分析是该公司正在探索未来商业产品的其他领域。。

James framed his experience with nanovials as a collaboration that began with Di Carlo's lab and continued with Partillion. He noted that he did a lot of troubleshooting early on alongside de Rutte. Issues included non-specific binding to the particles and cell loading issues, including loading efficiency.

詹姆斯将他在纳米瓶方面的经验描述为一种合作,从迪卡罗的实验室开始,并继续与Partillion合作。他指出,他在早期和德鲁特一起做了很多故障排除。问题包括与颗粒的非特异性结合和细胞负载问题,包括负载效率。

However, he said the company has been optimizing these aspects of its technology. .

然而,他表示,该公司一直在优化其技术的这些方面。

In May, James posted a preprint to BioRxiv with Di Carlo and UCLA epigenetics researcher Kathrin Plath on the use of nanovials to link single-cell transcriptomes with secretion. They used the method, dubbed 'Secretion amount of a target protein encoded by thousands of single cells with transcriptional sequencing (SEC-seq)' to link T-cell receptor sequences to cytokine secretion amounts, surface marker gene expression in 'highly secreting' mesenchymal stromal cells, and plasma cell transcriptomes with high immunoglobulin secretion levels..

5月,詹姆斯与迪卡罗(DiCarlo)和加州大学洛杉矶分校(UCLA)表观遗传学研究人员凯瑟琳·普拉斯(KathrinPlath)在BioRxiv上发布了一份预印本,内容是关于使用纳米小瓶将单细胞转录组与分泌联系起来。他们使用这种被称为“通过转录测序(SEC-seq)由数千个单细胞编码的靶蛋白的分泌量”的方法,将T细胞受体序列与细胞因子分泌量、“高分泌”间充质基质细胞中的表面标记基因表达以及具有高免疫球蛋白分泌水平的浆细胞转录组联系起来。。

The authors used the 35 micron nanovials in their experiments, but noted that 10x's new GEM-X chips may be compatible with the larger, 50 micron nanovials. 'Additionally, other single-cell RNA sequencing technologies that rely on split-pool reactions and do not use microfluidic chips are also expected to be compatible,' they wrote.

作者在实验中使用了35微米的纳米小瓶,但指出10x的新GEM-X芯片可能与较大的50微米纳米小瓶兼容此外,其他依赖分裂池反应且不使用微流控芯片的单细胞RNA测序技术也有望兼容,”他们写道。

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James has several specific uses planned for nanovials. 'One of them is doing perturb-seq-like applications' introducing CRISPR guide libraries into B cells to explore regulatory regions that might affect protein secretion or cell differentiation. Another is simply optimizing secretion of therapeutic products.

其中之一是做类似扰动序列的应用,将CRISPR指导文库引入B细胞,以探索可能影响蛋白质分泌或细胞分化的调控区域。另一个是简单地优化治疗产品的分泌。

'We're finding that the primary sequence actually makes a huge difference in the amount of antibody that gets secreted. .

“我们发现,一级序列实际上对分泌的抗体量产生了巨大的影响。”。

Partillion's multicell tech could also help slot in amidst the drive to bridge single-cell studies with spatial ones. 'With spatial biology, there are so many interactions, it's sometimes hard to piece out what's important, [and] what's actually driving cause and effect between these different cell types,' he said.

Partillion的多细胞技术也有助于将单细胞研究与空间研究联系起来。

'Pairing them in a more purposeful way, being able to look at cells together, can help you unravel how cell-cell interactions are causing different gene expression [patterns.]'.

“以更有目的的方式将它们配对,能够一起观察细胞,可以帮助你解开细胞间相互作用如何导致不同的基因表达[模式]。