近日，由基因疗法先驱 Jim Wilson 创立的生物技术公司 iECURE 宣布完成了 6500 万美元的 A 系列延期融资 ，以将其用于治疗鸟氨酸转氨甲酰酶缺乏症的候选药物推进临床。

【资料图】

本轮由 NovoHoldings 和 LYFECapital 共同领投，Versant OrbiMe 跟投。2021 年 9 月， iECURE 筹集了由后两者领投的 5000 万美元 A 轮融资。新的资金将使 iECURE 通过初步的人体试验。但在此之前，首席执行官 Joe Truitt 称会先计划将其员工人数增加一倍，目前有 12 名全职成员，包括聘请一名 CMO，为临床试验做准备。

iECURE 源于 “肝脏” 的拉丁文 “iecur”，“我们在词尾添加了 e，意味着治愈。” Joseph Truitt 表示。自 iECURE 成立后，Truitt 就被聘请担任 CEO，此前，他在 Achillion Pharmaceuticals（已被收购）工作 11 年，曾担任 CEO。

宾夕法尼亚大学和 Wilson 共同持有 iECURE 的股份。根据 iECURE 与宾夕法尼亚大学的协议，Wilson 实验室将对 iECURE 选定的管线进行临床前研究和制造，以及毒理实验，进入新药申请阶段时，将由 iECURE 接管并进行临床开发，如果获得批准，将进行商业化。

此外， Precision Bio 也获得了 iECURE 的部分股份。该公司已经 iECURE 达成合作开发同种异体 CAR-T 和体内基因疗法。

事实上， Wilson 和 Precision Bio 早有合作。过去 5 年，Wilson 和他的团队一直在研究生物体内对肝细胞基因组进行切割，然后插入正常的基因的相关机制。自从 80 年代后期他在实验室担任博士后以来，Wilson 就认为 肝脏是基因治疗的一个重要目标。 “因为很多疾病的根源都在肝脏。”Wilson 曾表示。

▲ 图 | iECURE 研发进展（来源：公司官网）

Wilson 及团队尝试了包括 CRISPR 在内的各种基因编辑工具，但收效甚微，直到使用 Precision Bio 的技术。这家位于北卡罗莱纳州的生物技术公司开发了一种名为 ARCUS 的平台。

ARCUS 是一个独特的、专有的、多功能的基因组编辑平台，其属性包括特异性、进行各种有效编辑（敲入、敲除和修复）的能力，从而实现一系列治疗性编辑。该平台基于一种称为 I-CreI 的天然基因组编辑酶，该酶从衣藻中进化而来，是一种归巢核酸内切酶，可以在细胞 DNA 中进行高强度特异性切割。

归巢核酸内切酶是一种非常罕见的内切酶，它们可以识别的 DNA 序列比经典的限制酶识别的范围要大。与基因编辑研究中的其它酶相比，I-CreI 酶仅有 364 个氨基酸，可用于插入、删除或者编辑 DNA。这也意味着，I-CreI 酶更容易被 AAV 递送。

此次将推进临床的鸟氨酸氨甲酰基转移酶缺乏会导致血液中氨浓度升高，婴儿通常会在出生后几天内出现症状。对于临床试验，治疗必须在非常小的时候进行——不到 8 个月。出于这个原因， iECURE 的非人类灵长类动物测试是在新生灵长类动物身上进行，以应对必须在非常小的年龄的患者上进行治疗这一事实。

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关键词： 临床试验 基因疗法