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用于亲肿瘤靶向和癌症基因治疗的全胶原克洛维斯点的出现:一项回顾性研究

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

作者信息

Gordon Erlinda M, Hall Frederick L

机构信息

Counterpoint Biomedica LLC, Santa Monica, CA, United States.

Delta Next-Gene, LLC, Santa Monica, CA, United States.

出版信息

Front Mol Med. 2023 Feb 28;3:1125928. doi: 10.3389/fmmed.2023.1125928. eCollection 2023.

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 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.

摘要

“克洛维斯尖状器”——石器时代工具技术中一项具有推动作用的史前功能获得,它使古印第安裔美国人能够更高效地狩猎、深入打击并杀死指定目标大型动物——是通过分子遗传生物工程生化制造出来的。这种生物医学“克洛维斯尖状器”是通过将在血管性血友病因子未成熟前原肽段中发现的广谱泛胶原蛋白结合域(Pan-Coll/CBD)改编成一系列先进的医学应用而制成的。经过实验、临床前和临床开发,成为一个前沿生物技术平台,克洛维斯尖状器适用于:1)在胶原支架上固态结合生长因子以改善骨科伤口愈合;2)促进受损/患病组织的再生;3)自体干细胞捕获、扩增和基于基因的治疗。随后对高亲和力Pan-Coll/CBD(暴露胶原寻找/监测功能)进行改编以用于人体静脉内给药,实现了生理递送,即对患病组织的趋病靶向——基因载体的修饰包膜;实现了4)癌症基因治疗的精准肿瘤靶向和5)过继性/局部免疫治疗,显示出改善的长期生存价值——从而开创了癌症管理中一个近端且可及的细胞周期控制点——使现代医学肿瘤学家能够解决化疗耐药、复发和转移性疾病隐匿进展等持续存在的问题。最近的工程改编提高了临床效用,包括小分子活性药物成分的靶向递送:包括紫杉烷、单克隆抗体和基于RNA的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ae4/11285703/eea469c12372/fmmed-03-1125928-g001.jpg

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