Transgenic silkworms producing sericin cocoons applicable for tissue engineering

Eiji Kotnai, H. Mori
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Abstract

Specific gene functions have been successfully suppressed by gene silencing or editing in many organisms. However, genetic manipulation to suppress the function of a target tissue has not been achieved using genes such as cytotoxin family members. We established transgenic silkworms with posterior silk glands (PSGs) that express the enzymatic domain of the cytotoxin pierisin-1A (P1A), a recently identified cytotoxic protein from the cabbage butterfly Pieris rapae , which has a relatively lower DNA ADP-ribosylating activity among the pierisin family. Larvae with the modified PSGs produced sericin cocoons with potential utility in tissue engineering. Our observations of an embryonic stem (ES) cell proliferation on fabricated sericin hydrogels demonstrated that such gels can act as a scaffolds to support cell growth and also mimic extracellular matrices to provide cell growth factors. In this highlight paper, we describe a new approach through targeted P1A expression, which could be applicable to the development of biologically-useful model organisms with tissue-specific dysfunction.
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用于组织工程生产丝胶茧的转基因蚕
在许多生物体中,通过基因沉默或编辑已经成功地抑制了特定的基因功能。然而,使用诸如细胞毒素家族成员的基因还没有实现抑制靶组织功能的基因操作。我们建立了具有后丝腺(PSG)的转基因蚕,其表达细胞毒素pierisin-1A(P1A)的酶结构域,这是一种最近从菜粉蝶中鉴定的细胞毒性蛋白,在pierisin家族中具有相对较低的DNA ADP核糖基化活性。使用改良PSG的幼虫生产出具有潜在组织工程实用性的丝胶茧。我们对胚胎干细胞(ES)在制备的丝胶水凝胶上增殖的观察表明,这种凝胶可以作为支架支持细胞生长,也可以模拟细胞外基质提供细胞生长因子。在这篇重点论文中,我们描述了一种通过靶向P1A表达的新方法,该方法可用于开发具有组织特异性功能障碍的生物有用的模式生物。
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