Pictured: An hourglass connected by strands of DNA/Nicole Bean for BioSpace

图为：一个沙漏，由DNA链/NicoleBean连接，用于BioSpace

Prime Medicine announced Monday that the FDA has cleared a study of a drug candidate based on its prime editing platform, marking the first time the agency has greenlit the use of the genetic technology in humans.

Prime Medicine周一宣布，FDA已经批准了一项基于其Prime编辑平台的候选药物研究，这标志着该机构首次在人类中使用基因技术。

Advocates of prime editing view the technology as an improvement on CRISPR/Cas9 and base editors. Unveiled in a Nature paper in 2019, the technology was designed to eliminate aspects of CRISPR that can cause health problems. Prime editors make changes without causing double-strand breaks, which can in theory lead to cancer and can make a wide range of edits such as substitutions, insertions and deletions..

prime编辑的倡导者将该技术视为对CRISPR/Cas9和基础编辑器的改进。该技术于2019年在《自然》杂志的一篇论文中公布，旨在消除CRISPR可能导致健康问题的方面。主要编辑在不引起双链断裂的情况下进行更改，从理论上讲，双链断裂可能导致癌症，并且可以进行广泛的编辑，例如替换，插入和删除。。

Prime Medicine is at the forefront of efforts to use the technology to treat disease. The FDA clearance of an application to test the ex vivo candidate PM359 in chronic granulomatous disease (CGD) positions the biotech to run the first human study of prime editing.

Prime Medicine处于使用该技术治疗疾病的最前沿。FDA批准了一项在慢性肉芽肿性疾病（CGD）中测试离体候选PM359的应用程序，这使该生物技术公司能够进行首次人体初步编辑研究。

CGD is caused by mutations in the p47phox protein. Patients have recurrent, life-threatening bacterial and fungal infections that are difficult to eradicate. Allogeneic hematopoietic stem cell transplantation can cure the condition but access to the treatment is limited. Patients who do receive transplants are at risk of graft-versus-host disease and graft failure..

CGD是由p47phox蛋白突变引起的。患者患有复发性，威胁生命的细菌和真菌感染，难以根除。异基因造血干细胞移植可以治愈这种疾病，但获得治疗的机会有限。确实接受移植的患者有移植物抗宿主病和移植物衰竭的风险。。

Prime Medicine makes PM359 by using prime editors to correct the patient’s own hematopoietic stem cells outside of the body. In preclinical tests, edited cells repopulated the bone marrow and restored the enzyme at the root of the rare disease.

Prime Medicine通过使用Prime编辑器在体外纠正患者自身的造血干细胞来制造PM359。在临床前测试中，经过编辑的细胞重新填充了骨髓，并恢复了这种罕见疾病根源的酶。

The biotech will evaluate the candidate in three small cohorts in a Phase I/II trial, starting with people aged 18 years and over who have stable disease. Later cohorts will test PM359 in people aged as young as six years and in participants with active infection or severe inflammation. Prime Medicine will track endpoints including early markers of restored immune function and aims to share the first clinical data in 2025..

该生物技术公司将在I/II期试验的三个小组中对候选人进行评估，从18岁及以上疾病稳定的人群开始。后来的队列将在6岁以下的人群以及活动性感染或严重炎症的参与者中测试PM359。Prime Medicine将跟踪终点，包括恢复免疫功能的早期标志物，并旨在在2025年分享第一份临床数据。。

Like some CRISPR biotechs before it, Prime Medicine has picked an ex vivo application as the first use of its platform but has a pipeline that skews toward in vivo therapies. In vivo editing eliminates the need to remove and re-administer cells but altering DNA inside humans also creates additional risks.

像之前的一些CRISPR生物技术一样，Prime Medicine选择了离体应用作为其平台的首次使用，但其管道偏向于体内治疗。体内编辑消除了去除和重新管理细胞的需要，但改变人体内的DNA也会产生额外的风险。

Off-target edits could have long-term negative effects on health..

脱靶编辑可能会对健康产生长期负面影响。。

Prime Medicine is developing candidates that use lipid nanoparticles (LNP) and adeno-associated virus vectors to deliver prime editors. The biotech is working on a range of diseases that affect the liver, eye, nervous system and other parts of the body. IND-enabling activities are scheduled to start this year, putting Prime Medicine on track to study a LNP liver candidate in humans around the end of 2025..

Prime Medicine正在开发使用脂质纳米颗粒（LNP）和腺相关病毒载体来提供Prime编辑器的候选药物。这项生物技术正在研究一系列影响肝脏、眼睛、神经系统和身体其他部位的疾病。IND启用活动计划于今年开始，使Prime Medicine有望在2025年底左右研究人类LNP肝脏候选物。。

Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.

尼克·保罗·泰勒（NickPaulTaylor）是一位自由职业的制药和生物技术作家，总部位于伦敦。可以通过LinkedIn联系到他。