ENLIGHT : Light-sensitive Engineered Living Material for acne therapy

2019年，寻常痤疮的患病率为2.5亿人，已成为全球最大的皮肤负担和全球第八大流行疾病。痤疮是一种慢性炎症性疾病，其治疗方案具有重要的副作用。例如，抗生素导致超级细菌的发展。维甲酸仍然是治疗的首选，但迫切需要新的输送形式，以提高其疗效，避免与口服摄入相关的副作用。我们的愿景是开发一种新型的工程生物材料（ELMs）用于痤疮治疗。ELM是一种“智能”材料，它将活细胞与惰性基质联合收割机结合起来。本提案旨在开发一种适用于痤疮治疗的光响应ELM，其使用细菌纳米纤维素（BNC）和光遗传工程乳酸乳球菌原位产生视黄酸。L.乳酸菌是一种益生菌，通常被认为是安全的（GRAS），以前被宿主组用于细胞工程。BNC具有完全生物相容性、透明性和优异的机械性能。这种ELM将允许使用蓝光（一种正交和非侵入性的输入，可以很容易地应用和停止）进行精确的时空控制。这种ELM的开发完全符合绿色化学原理，并将利用BNC与L.乳酸被工程化以原位递送视黄酸（避免其降解）。这种蓝光响应ELM将是皮肤治疗中的有价值的工具，并且将在存在痤疮皮肤杆菌（Cutibacterium acnes）的情况下在人类皮脂腺细胞模型中进行测试，痤疮皮肤杆菌是一种参与痤疮疾病发病机制的细菌。此外，这种ELM在治疗其他皮肤病中非常相关，而且在食品工业和化妆品中也非常相关，因为对视黄酸的前体（例如，β-胡萝卜素、番茄红素、维生素A）。

With a prevalence of 250 million people in 2019, acne vulgaris has emerged as the greatest global skin burden and the 8th most prevalent disease worldwide. Acne is a chronic inflammatory disease whose treatment options have important side-effects. For example, antibiotics lead to the development of superbugs. Retinoic acid continues to be the treatment of choice but novel forms of delivery are urgently needed to improve its efficacy and avoid side-effects associated to oral uptake.Our vision is to develop a novel class of Engineered Living Materials (ELMs) for acne treatment. ELMs are "smart" materials that combine living cells with inert matrices. This proposal aims at developing a light-responsive ELM suitable for acne therapy using Bacterial Nanocellulose (BNC) and Optogenetically Engineered Lactococcus lactis to produce retinoic acid in situ. L. lactis is a probiotic Generally Recognised as Safe (GRAS) previously used by the host group in cell engineering. BNC is fully biocompatible, transparent, and with superb mechanical properties. This ELM will allow precise spatiotemporal control using blue light (an orthogonal and non-invasive input that can be easily applied and stopped). The development of this ELM can be fully framed in the Green Chemistry principles, and will take advantage of the synergistic properties of BNC combined with L. lactis engineered to deliver retinoic acid in situ (avoiding its degradation). This blue light-responsive ELM will be a valuable tool in skin treatment, and will be tested in human sebocyte models in the presence of Cutibacterium acnes, a bacterium involved in the pathogenesis of acne condition. Furthermore, this ELM will be very relevant in the treatment of other skin conditions, but also in food industry and cosmetics, as there is broad interest in the precursors of retinoic acid (e.g., beta-carotene, lycopene, vitamin A).