Healing Tissues via Programmable DNA Nanotechnology

生长因子是细胞产生和释放的强大生物蛋白质。它们在指导我们的细胞如何从一个卵子细胞生长成大约30万亿个细胞中起着关键作用，这些细胞以协调的方式排列，以创造一个人。它们的影响也会持续到我们的一生;如果组织受损，例如骨折或皮肤上的伤口，生长因子会协调我们的组织愈合。由于这种强大的影响力，生长因子是非常有吸引力的物质，可用作促进组织修复的治疗剂。虽然有几种药物在世界各地的诊所中使用，但由于次优疗效和高生产成本，它们的疗效、安全性和影响都远远不是最佳的。因此，为了真正实现其作为治疗剂的潜力，我们需要新的策略来彻底改变我们在临床上使用生长因子的方式。 在这个提案中，我们将联合收割机方面的材料科学，纳米技术和生物学开发一个转型的方法来使用生长因子作为治疗。我们的方法依赖于设计新的纳米技术材料，这些材料可以从体内积极收获生长因子，然后用作治疗剂来治愈组织。这一策略将消除生产昂贵蛋白质的需要，从而大大降低治疗成本。此外，它将使以前批准的治疗方法适应组织修复的新领域，加快新治疗方法的开发，同时最大限度地降低生产成本。 我们将展示我们的新方法治愈临界尺寸骨缺损的能力-即，骨缺损太大而无法自行自然愈合。这些数据构成了证明将其转化为临床的关键组成部分，使这一提议有助于将这种令人兴奋的新技术带到床边。

Growth factors are powerful biological proteins that cells produce and release. They have a key role in instructing our cells how to grow from one cell as an egg into approximately 30 trillion cells that are arranged in a coordinated fashion to create a person. Their influence also continues throughout our lives; if tissues are damaged such as a broken bone or wound on our skin, growth factors coordinate how our tissue heal. Because of this powerful influence, growth factors are highly attractive substances to use as therapeutics to promote tissue repair. While several are used in clinics around the world, their efficacy, safety, and impact are all far from being optimal due to sub-optimal efficacy and a high cost of production. Therefore, in order to truly realise their potential as therapeutics, we need new strategies that revolutionise how we use growth factors clinically. In this proposal, we will combine aspects of materials science, nanotechnology, and biology to develop a transformational approach to using growth factors as therapeutics. Our approach relies on designing novel nanotechnology-enabled materials that actively harvest growth factors from within the body to then use as therapeutics to heal tissues. This strategy will eliminate the need to produce expensive proteins, dramatically reducing the cost of treatment. Furthermore, it will enable the adaptation of previously approved therapeutics to new areas in tissue repair, speeding up the development of new treatments while also minimising production expenses. We will demonstrate the ability of our new approach to heal critical size bone defects - that is, bone defects that are too large to naturally heal on their own. This data forms a key component of justifying the translation to the clinic, making this proposal instrumental in bringing this exhilarating new technology to the bedside.