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In the long-standing battle between humans and viruses, the continuous mutation of viruses resembles an arms race where “as virtue rises one foot, vice rises ten.” As the shadow of the COVID-19 pandemic gradually recedes, we are still not entirely free from the threat posed by coronaviruses. The emergence of new viral variants continues to challenge global public health security. Against this backdrop, a research team comprising multiple world-renowned institutions, including the University of Pittsburgh, has successfully screened a type of pan-sarbecovirus nanobody (psNbs) with "super immunity" from immunized alpacas using innovative technological approaches. This study, published in Cell Reports, aims to identify a universal solution capable of combating an entire virus family.

In plant biology research, deciphering protein localization, interactions, and dynamics is central to unraveling life's mechanisms. Traditional protein tagging techniques relying on fluorescent proteins or epitope tags are often hindered by large tag size, insufficient affinity, or limited applicability. This is particularly problematic for "hard-to-tag" proteins such as multi-pass transmembrane proteins (e.g., metal transporters) and functionally sensitive proteins, where traditional methods can disrupt their structure and function, bringing research to a halt. Nanobodies, with their advantages of high affinity and genetic encodability, offer a potential solution to this bottleneck. While the ALFA tag and ALFA nanobody system have previously demonstrated excellent performance in animal and yeast cells, their applicability in plants had not been systematically evaluated.

大肠杆菌同样是一种以原核表达体系为基础的展示技术。将抗体或其他类型展示在大肠杆菌表面的方式灵活多样，根据不同的筛选方式，可以将抗体展示在外膜上直接同抗原结合，或展示在细胞周质中，在破碎细胞外膜后再同抗原结合。纳米抗体相对简单的结构使其非常适合这种展示技术。大肠杆菌展示也具有库容量大的特点，其库容量也可以达到1E10级别，对抗体库的覆盖程度很高。虽然大肠杆菌作为一种原核生物，PTM同人类相差较大，但大肠杆菌生长迅速，培养简单，因此大肠杆菌展示的技术周期较短；相比噬菌体展示，大肠杆菌展示可在上游进行高亲和力富集之后再进行筛选，进一步提高抗体序列特异性，同时提高下游筛选得到高亲和力抗体的可能性。纳博生命科技的NabLib®抗体发现平台向客户提供高效的大肠杆菌展示为基础的抗体发现及抗体工程服务，助力抗体药物开发。

噬菌体展示技术迄今已经有60年的历史，是最早应用于抗体筛选的展示技术。噬菌体展示是通过将待改造的抗体或其他类型的蛋白构建在病毒表面蛋白上来实现的，如pIII、pVIII、pVII、pVI以及pIX蛋白。其中最常用的是pVIII，因为该蛋白在噬菌体表面有大约3000个拷贝，可以大大增强检测信号。噬菌体展示技术最大的优势是库容量大，可以达到1E10-1E11级别，能够轻易地满足免疫库或突变库的库容需求，有利于抗体的筛选。依托大肠杆菌原核表达体系，噬菌体展示技术虽然无法在抗体成药性和序列特异性方面同哺乳动物细胞展示技术相比，但凭借相对简单的实验操作步骤，更短的技术周期，自问世以来即成为问世以来经久不衰的筛选技术。纳博生命科技的NabLib^®抗体发现平台提供高效的噬菌体展示为基础的抗体发现及抗体工程服务，助力抗体药物开发。

多跨膜蛋白作为最常见的药靶蛋白。由于跨膜次数多，胞外区(Extracellular domain;ECD)结构松散，往往难以像单次跨膜蛋白一样以ECD的形式纯化后用作免疫原或筛选原。多跨膜蛋白的跨膜区疏水性强，可以通过去垢剂进行纯化;但是去垢剂难以去除的缺点使得这种方式纯化的多跨膜蛋白并不适合作为免疫原使用。为此，纳博生命科技开发了独特的病毒样颗粒(VLP)和纳米圆盘(Nanodisc)技术平台，解决多跨膜蛋白免疫原/筛选原的技术问题。VLP通过病毒衣壳出芽过程实现对过表达的膜蛋白的富集。衣壳蛋白在细胞膜附近聚集形成球形衣壳，在出芽的过程中将宿主细胞膜包裹在外围，形成携带了宿主细胞膜及膜上蛋白的VLP。Nanodisc则应用了完全不同的原理，通过MSP或SMA形成多聚物，将细胞膜分割成~10nm直径的纳米级圆盘，使得每个圆盘上仅能容纳1个多跨膜蛋白，提高了膜蛋白的纯度。