An amphipathic reagent to extract stabilize and purify proteins

在过去的二十年里，新的治疗剂的发展经历了一场革命。80年来，药物几乎完全由相对较小的化学物质组成。然而，生物治疗药物最近已成为正在开发的增长最快的新药类型。它们包括抗体，这些抗体是我们身体免疫系统的一部分，可以抵御感染。抗体是一种被称为蛋白质的分子；与过去用于药物的化学物质相比，这些蛋白质非常复杂和非常脆弱。大多数临床使用的生物治疗剂是在微生物中制造的药物或由活生物产生的物质。它们包括抗体和酶。大多数生物技术药物都是通过基因工程产生的重组蛋白质。具体的例子包括胰岛素和干扰素等细胞因子、抗囊性纤维化的重组酶(阿尔替普酶)、激素(促红细胞生成素和人类生长激素)、凝血因子、疫苗和单抗。生物技术制药有很大的局限性。许多很难原封不动地提纯，而且保质期有限，不稳定。此外，有些药物不能通过胃肠道、肺部或皮肤吸收。杂质也是一个常见的问题，因为它们大多是从复杂的生物来源提纯的。蛋白质杂质会引起过敏反应或改变治疗效果。因此，生产稳定的、易于提纯的蛋白质颗粒是非常重要的。我们已经开发了一种新的解决方案，可以同时提高生物治疗剂的产量和稳定性。提供这种溶液的化学物质(称为SPS)可以以两种方式起作用，帮助生产某些生物疗法药物。首先，它可以用来帮助产品从生产它的微生物中释放出来。一旦释放，SPS就像一个稳定的手镯，包裹在水中通常不稳定的蛋白质周围，防止它们失去活性。这两种能力都将极大地提高生物治疗生产的效率，这应该会导致更便宜和更多可用的药物。作为一个额外的优点，该试剂在人体内使用是安全的，并已被证明有助于药物进入人体，提高它们的有效性。这再次具有降低药品成本的潜力。该项目旨在展示SPS在生物治疗开发中的有效性，同时开发协议，以便它可以很容易地被生物治疗公司采用。

The development of new therapeutic agents has undergone a revolution during the last two decades. For 80 years medicines have almost exclusively consisted of relatively small chemicals. However, biotherapeutics agents have recently emerged as the fastest growing type of new drugs being developed. They include antibodies that are part of our body's immune systems that fight off infections. Antibodies are a type of molecule called a protein; these proteins are highly complex and very fragile in contrast to the chemicals that were used in medicines in the past. Most biotherapeutic agents in clinical use are drugs manufactured in microorganisms or substances that are produced by living organisms. They include antibodies and enzymes. Most biotech pharmaceuticals are recombinant proteins produced by genetic engineering. Specific examples include cytokines like insulin and interferons, recombinant enzymes that combat cystic fibrosis (dornase alfa) and heart disease (Alteplase), hormones (Erythropoietin and human growth hormone), clotting factors, vaccines and monoclonal antibodies. Biotech pharmaceuticals have major limitations. Many are difficult to purify intact, and are unstable with limited shelf lives. Also, some are not absorbable in a medically useful form through the gastrointestinal tract, lungs or skin. Impurity is also a common problem, as they most be purified from complex biological sources. Protein impurities can cause allergic reactions or alter therapeutic effects. Hence, production of a stable protein particle that can easily be purified is very important. We have developed a new solution that increases both the yield and stability of the biotherapeutic. The chemical (called SPS) that provides this solution can act in two ways that helps the production of certain biotherapeutcics. Firstly it can be used to help release the product from the microorganisms in which it has been made. Once released the SPS can act like a stabilising bracelet, wrapping around proteins that are not generally stable in water preventing them from loosing activity. Both of these abilities will greatly increase the efficiency of biotherapeutic production which should result in cheaper and more available drugs. As an added advantage the reagent is safe for use in human beings and has been shown to facilitate the uptake of drugs into the body, increasing their effectiveness. This again has the potential to reduce drug costs. This project aims to demonstrate the effectiveness of SPS in biotherapeutic development while at the same time develop protocols so that it can be easily adopted by companies making biotherapeutics.