Exploiting Controlled Environments for the Development of Optimised Cannabis Sativa Phenotypes for Pharmaceutical Applications - CE-CannPharm

制药业相对成熟，有太多日益尖端的科学、技术和最近的人工智能方法支撑。尽管90%的临床药物开发失败了，但全球人口结构的变化正在推动退行性和神经退行性/功能障碍疾病的数量增加，这使得制药公司将他们的重点扩大到基于自然的疗法，并在这里接受了众所周知的、越来越有临床基础的医用大麻的好处。英国下议院图书馆最近的一份研究简报指出，英国是世界上最大的用于医疗和科学目的合法大麻的生产国和出口国，禁止合作伙伴预测到2026年，英国的价值将达到10亿GB，Statista估计全球市场的收入已经超过130亿GB。然而，制药业的大麻有一个问题，即大麻类物质的分布随植物中的位置而变化，顶部、中部和底部的花的化学分布显示出+/-20%(或更多)的数量级变化，这大大超过了典型的制药产品=+/-10%的容忍度。这对被认为是药用的花生米造成了一个严重的一致性和分级问题。在这里，我们与我们的行业合作伙伴Glass Pharms Ltd，旨在通过几个途径来解决这个问题。通过筛选不同的花卉种质，我们将建立植物结构变异，目的是探索最终创造出具有不同结构的花卉植物的潜力：较少的“圣诞树”-更多的“烛台”形状，花序(花)更均匀地呈现在入射光线下。这应该会对花卉的生物活性成分和重要的差异补偿产生积极的影响。我们还将寻求通过现有方法使紫花苜蓿变矮来提高生产力和减少差异，并探索通过垂直耕作实现完全控制的环境农业的潜力。这种对环境的绝对控制将使我们能够在整个作物发展过程中充分利用VF嵌入灯的可调光强度和波长，从而也有机会“调整”大麻类大麻和萜类化合物的含量、组成和变化。为此，我们将在基因和代谢物水平上阐明光/植物的相互作用，以确定重要的基因级联，以期通过传统或现代(基因修改/基因编辑)育种方法确定基因靶标/标记，用于未来的开发。以下是JHI和Glass Pharms Ltd之间合作的一部分，这两家公司都是高TCH大麻生产许可证的持有者，我们将实现以下目标：极大地改善大麻中所含有效药物成分在同一植物上不同花序(花)中分布的一致性。更好地标准化CAE/VF系统的品种表型，目标是矮小和统一的表型。定义条件和过程，以操纵/定义大麻素的含量和组成。在更广泛的背景下，这项计划中的研究支持了英国的许多政策目标，包括高价值部门经济增长、相关的永久性高技能工作、为不断变化的人口改善医疗保健以及英国农业基础的多样化。这项拟议中的科学将巩固并帮助保持英国作为医用大麻生产国和出口国的领先地位。

The pharmaceutical industry is relatively mature and underpinned with a plethora of increasing sophisticated science, technology, and more recently, AI approaches. Despite this 90% of clinical drug development fails but global demographic evolution is driving increased numbers of degenerative and neurodegenerative/dysfunctional disease, and this has seen pharma broaden their focus to nature-based therapies and, here, embrace the long-known, and increasingly clinically underpinned, benefits of medicinal cannabis.A recent research briefing from the House of Commons Library report identified that the UK is the world's biggest producer and exporter of legal cannabis for medical and scientific purposes with Prohibition Partners projecting a UK value of £1Bn by 2026 and Statista estimating a global market already in excess of £13Bn in revenue.However, there is a problem with cannabis for the pharmaceutical industry in that the cannabinoid profile changes with location in the plant with the chemo-profiles of the flowers at the top, middle and bottom showing a variance of an order of +/-20% (or more), which is significantly beyond a typical pharmaceutical product tolerance of =+/-10%. This creates a major consistency and grading problem for C.Sativa when it is considered as a pharmaceutical medicine.Here, with our industry partners Glass Pharms Ltd, we aim to address this via several avenues. Via a screen of diverse C.Sativa germplasm we will establish plant architecture variation with the aim of exploring the potential of ultimately creating C.Sativa plants with an altered architecture: less "Christmas tree"- and more "menorah"-shaped, with inflorescence (flowers) more even presented to the incident light. This should impact positively on flower bioactive content composition and importantly variance redcution.We will also look to increase productivity and reduced variance by dwarfing C.Sativa through established methods and exploring the potential of total controlled environmental agriculture here by vertical farming. This absolute control on the environment will allow us to fully exploit the tuneable light intensity and wavelengths of the VF-embedded lights across crop development offering the opportunity to also "tune" the cannabis cannabinoid and terpenoid content, composition and variance. Allied to this we will elucidate the light/plant interactions at the gene and metabolite levels to identify the important gene cascades with a view to identifying gene targets/markers for future exploitation via traditional or modern (genetic modification/gene editing) breeding approaches.Here as part of a collaboration between JHI and Glass Pharms Ltd, both high TCH cannabis production licence holders, we will deliver the following: Greatly improved consistency in the distribution of the active pharmaceutical ingredients contained in Cannabis Sativa across different inflorescence (flowers) on the same plant.Better standardisation of cultivar phenotypes for CAE/VF systems with a target for dwarfed and uniform phenotypes.Defined conditions and process to manipulate/define cannabinoid content and composition. In a wider context the planned research underpins many of the UK policy targets in terms of high-value sector economic growth with associated permanent highly skilled jobs, improvement of healthcare for an evolving demographic and the diversification of the UK agricultural base. The proposed science here will underpin and help maintain the UK's lead as a medicinal cannabis producer and exported.