The advent of a pan-collagenous CLOVIS POINT for pathotropic targeting and cancer gene therapy, a retrospective.

Frontiers in molecular medicine Pub Date : 2023-02-28 eCollection Date: 2023-01-01 DOI:10.3389/fmmed.2023.1125928
Erlinda M Gordon, Frederick L Hall
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Abstract

The 'Clovis Point'-an enabling prehistoric gain-of-function in stone-age tool technologies which empowered the Paleoindian-Americans to hunt, to strike-deep, and to kill designated target megafauna more efficiently-was created biochemically by molecular-genetic bio-engineering. This Biomedical "Clovis Point" was crafted by adapting a broad-spectrum Pan-Collagen Binding Domain (Pan-Coll/CBD) found within the immature pre-pro-peptide segment of Von Willebrand Factor into a constructive series of advanced medical applications. Developed experimentally, preclinically, and clinically into a cutting-edge Biotechnology Platform, the Clovis Point is suitable for 1) solid-state binding of growth factors on collagenous scaffolds for improved orthopedic wound healing, 2) promoting regeneration of injured/diseased tissues; and 3) autologous stem cell capture, expansion, and gene-based therapies. Subsequent adaptations of the high-affinity Pan-Coll/CBD (exposed-collagen-seeking/surveillance function) for intravenous administration in humans, enabled the physiological delivery, aka Pathotropic Targeting to diseased tissues via the modified envelopes of gene vectors; enabling 4) precision tumor-targeting for cancer gene therapy and 5) adoptive/localized immunotherapies, demonstrating improved long-term survival value-thus pioneering a proximal and accessible cell cycle control point for cancer management-empowering modern medical oncologists to address persistent problems of chemotherapy resistance, recurrence, and occult progression of metastatic disease. Recent engineering adaptations have advanced the clinical utility to include the targeted delivery of small molecule APIs: including taxanes, mAbs, and RNA-based therapeutics.

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泛胶原CLOVIS POINT用于致病性靶向和癌症基因治疗的出现,回顾
“克洛维斯角”是通过分子遗传生物工程在生物化学上创造的,它使史前石器时代的工具技术得以发挥作用,使古印度裔美国人能够更有效地狩猎、深入打击和杀死指定的目标巨型动物。这种生物医学“Clovis Point”是通过将Von Willebrand因子的未成熟前肽段中发现的广谱泛胶原蛋白结合结构域(Pan-Coll/CBD)应用于一系列建设性的高级医学应用而制成的。Clovis Point经过实验、临床前和临床开发成为尖端的生物技术平台,适用于1)生长因子在胶原支架上的固态结合,以改善骨科伤口愈合,2)促进损伤/病变组织的再生;以及3)自体干细胞捕获、扩增和基于基因的治疗。随后,高亲和力Pan-Coll/CBD(暴露的胶原寻找/监测功能)适应于人类静脉给药,使得能够通过基因载体的修饰包膜向病变组织进行生理递送,也称为病理靶向;实现4)用于癌症基因治疗的精确肿瘤靶向和5)采用/局部免疫疗法,通过开创癌症管理的近端和可接近的细胞周期控制点,显示出改善的长期生存价值,使现代医学肿瘤学家能够解决化疗耐药性、复发、,转移性疾病的隐性进展。最近的工程改造提高了临床实用性,包括小分子API的靶向递送:包括紫杉烷、单克隆抗体和基于RNA的治疗方法。
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