ENLIGHT : Light-sensitive Engineered Living Material for acne therapy

2019年，寻常痤疮的患病率为2.5亿人，已成为全球皮肤负担最大的疾病和全球第八大最流行的疾病。痤疮是一种慢性炎症性疾病，其治疗方案有重要的副作用。例如，抗生素会导致超级细菌的发展。维甲酸仍然是治疗痤疮的首选药物，但迫切需要新的给药形式来提高其疗效，避免与口服摄取相关的副作用。我们的愿景是开发一类用于治疗痤疮的新型工程生物材料(ELMS)。榆树是将活细胞和惰性基质结合在一起的“智能”材料。这项建议旨在利用细菌纳米纤维素(BNC)和光基因工程乳酸乳球菌原位生产维甲酸来开发一种适用于痤疮治疗的光响应型ELM。乳酸乳杆菌是一种被普遍认为是安全的益生菌(GRAS)，以前曾被宿主组用于细胞工程。BNC具有完全的生物相容性、透明性和卓越的机械性能。这种ELM将允许使用蓝光(一种易于应用和停止的正交和非侵入性输入)进行精确的时空控制。这种ELM的开发完全符合绿色化学原则，并将利用BNC与乳酸结合的协同特性，该乳酸被设计为原位输送维甲酸(避免其降解)。这种蓝光响应型ELM将成为皮肤治疗的有价值的工具，并将在人类皮脂细胞模型中进行测试，其中存在痤疮皮肤杆菌，一种参与痤疮发病机制的细菌。此外，这种榆树将非常相关的其他皮肤疾病的治疗，但也在食品工业和化妆品，因为人们对维甲酸的前体(例如，β-胡萝卜素，番茄红素，维生素A)有广泛的兴趣。

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).