Novel Nanosyringes for biologic delivery: understanding immune profile and applications in genetic engineering

细菌是优秀的细胞生物学家：他们已经操纵动物细胞超过20亿年了，而人类这样做只有几十年。因此，细菌有很多东西可以教给我们。我们已经发现，某些细菌产生一种非凡的“分子注射器”，它预先装载了特定的“货物”蛋白质，它们用来操纵宿主动物的细胞活动。它们代表着一个非常高效和优雅的系统，在细菌释放到周围环境之前在细菌内部自我组装。一旦识别出来，它们就会使用抗体样的手臂(通常被称为“结合纤维”)来识别特定的“靶”动物细胞。它们与细胞表面结合，并将它们的货物蛋白直接注入细胞内部。基于蛋白质的药物，即所谓的生物制药，在过去20年里改变了这个行业，成为当前治疗工具箱的主要组成部分，具有巨大的收入价值。然而，除了少数例外，将功能性蛋白质直接输送到感兴趣的细胞内是极其困难的，这严重阻碍了它们的实用性。例如，作为生物制药的最新革命，代表大多数药物的单抗主要结合细胞外或细胞表面靶标。目前的估计预测，我们只给人类总蛋白质补体的10%下药，其中大部分是细胞表面的。目前确实存在各种将蛋白质带入细胞的策略，但它们通常会受到严重的限制。例如，纳米技术衍生的化学聚合物通常是无靶向的，不能提供明确剂量的货物蛋白。我们的“纳米注射器”技术规定的货物剂量和特定的细胞靶向结合纤维，意味着它们可以更优雅地满足将蛋白质输送到细胞内的未满足需求。本质上就像微小的皮下注射器，能够直接将有用的蛋白质注射到原本无法渗透的细胞膜上。蛋白质控制着细胞中的大多数活动，充当着运行大多数细胞过程的“分子引擎”。我们改装的纳米注射器将允许我们“深入”细胞的引擎盖下，提供修复或杀死表现出不想要的疾病状态(如癌症)的细胞所需的必要蛋白质“成分”。最终，我们的目标是开发这种首创的运载工具，以改善人类健康的治疗结果，并促进前沿生物科学，如基因工程、干细胞研究等。

Bacteria are excellent cell biologists: they have been manipulating animal cells for over 2 billion years, whereas humans have been doing so for just a few decades. Bacteria, therefore, have much to teach us. We have discovered that certain bacteria produce a remarkable 'molecular syringe' which is pre-loaded with specific 'cargo' proteins that they use to manipulate the cellular activity of host animals. They represent a very efficient and elegant system, self-assembling inside the bacteria before being released into the surroundings. Once out, they recognise their specific "target" animal cells using antibody-like arms, generally known as 'binding fibres'. They bind to the surface of the cell and inject their cargo protein directly into the interior. Protein-based drugs, so-called biopharmaceuticals, have transformed the industry over the last 20 years to become a major constituent of the current therapeutics toolbox with a huge revenue value. However, with only a handful of exceptions, it is extremely difficult to deliver functional proteins directly inside cells of interest, severely hampering their utility. For example, monoclonal antibodies which, as the most recent revolution in biopharmaceuticals represent the majority of drugs, predominantly bind extracellular or cell surface targets. Current estimates predict that we have only drugged as little as 10% of the total human protein complement, and most of these are cell surface. Various strategies do currently exist for getting proteins into cells, but they typically suffer serious limitations. For example, nano-technology derived chemical polymers are typically untargeted and cannot deliver a well-defined dose of cargo proteins. The defined cargo dose and specific cell targeting binding fibres of our 'nanosyringe' technology, means they can more elegantly fulfill the unmet need for delivery of proteins into the cell. Essentially acting like tiny hypodermic syringes, able to directly inject useful proteins across the otherwise impermeable cell membrane. Proteins govern the majority of activities in a cell, acting as the "molecular engine" running most cellular processes. Our modified nanosyringes will allow us to "get under the hood" of the cell, delivering the necessary protein 'components' required to either repair or kill cells exhibiting unwanted disease states, such as cancer. Ultimately, we aim to develop this first-of-its-kind delivery vehicle to improve therapeutic outcomes in human health, and to facilitate cutting edge bioscience such as gene engineering, stem cell research and much more.