公开(公告)号：US10370658B2

公开(公告)日：2019-08-06

申请号：US15442557

申请日：2017-02-24

申请人： Shi-Lung Lin ,  Donald C. Chang ,  David T S Wu ,  Hsuan-Hsuan Lu

发明人： Shi-Lung Lin ,  Donald C. Chang ,  David T S Wu ,  Hsuan-Hsuan Lu

IPC分类号： C12N15/113 ,  C12N15/11

摘要： This invention generally relates to a composition and method of using mam-made small RNAs, such as small interfering RNAs (siRNA), microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA), as tumor suppressing anti-cancer drugs for treating human tumors and cancers, in particular, but not limited, for treating skin (melanoma), blood (leukemia), prostate, breast, liver and lung cancers as well as various neoplastic tumors, such as brain tumors and teratocarcinomas that contain a variety of tumorous and cancerous cells derived from all three germ layers of tissues, including ectoderm, mesoderm and endoderm. More specifically, the present invention relates to the use of miR-302-like siRNA (siR-302) and/or miR-302 precursors (pre-miR-302) for developing novel medicines and therapies against a variety of human cancers, in particular lung cancers.

公开(公告)号：US20170175118A1

公开(公告)日：2017-06-22

申请号：US15442557

申请日：2017-02-24

申请人： Shi-Lung Lin ,  Donald C. Chang ,  David TS Wu ,  Hsuan-Hsuan Lu

发明人： Shi-Lung Lin ,  Donald C. Chang ,  David TS Wu ,  Hsuan-Hsuan Lu

IPC分类号： C12N15/113

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N15/1135 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2320/30 ,  C12N2320/32 ,  C12N2330/50 ,  C12N2330/51

摘要： This invention generally relates to a composition and method of using mam-made small RNAs, such as small interfering RNAs (siRNA), microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA), as tumor suppressing anti-cancer drugs for treating human tumors and cancers, in particular, but not limited, for treating skin (melanoma), blood (leukemia), prostate, breast, liver and lung cancers as well as various neoplastic tumors, such as brain tumors and teratocarcinomas that contain a variety of tumorous and cancerous cells derived from all three germ layers of tissues, including ectoderm, mesoderm and endoderm. More specifically, the present invention relates to the use of miR-302-like siRNA (siR-302) and/or miR-302 precursors (pre-miR-302) for developing novel medicines and therapies against a variety of human cancers, in particular lung cancers.

公开(公告)号：US20200165607A1

公开(公告)日：2020-05-28

申请号：US16532353

申请日：2019-08-05

申请人： Shi-Lung Lin ,  Donald C. Chang ,  David TS Wu ,  Hsuan-Hsuan Lu

发明人： Shi-Lung Lin ,  Donald C. Chang ,  David TS Wu ,  Hsuan-Hsuan Lu

IPC分类号： C12N15/113 ,  C12N15/11

摘要： This invention generally relates to a composition and method of using mam-made small RNAs, such as small interfering RNAs (siRNA), microRNAs (miRNA) and their hairpin-like precursors (pre-miRNA), as tumor suppressing anti-cancer drugs for treating human tumors and cancers, in particular, but not limited, for treating skin (melanoma), blood (leukemia), prostate, breast, liver and lung cancers as well as various neoplastic tumors, such as brain tumors and teratocarcinomas that contain a variety of tumorous and cancerous cells derived from all three germ layers of tissues, including ectoderm, mesoderm and endoderm. More specifically, the present invention relates to the use of miR-302-like siRNA (siR-302) and/or miR-302 precursors (pre-miR-302) for developing novel medicines and therapies against a variety of human cancers, in particular lung cancers.

公开(公告)号：US09394538B2

公开(公告)日：2016-07-19

申请号：US12792413

申请日：2010-06-02

申请人： Shi-Lung Lin ,  David T S Wu

发明人： Shi-Lung Lin ,  David T S Wu

IPC分类号： C12N15/11 ,  C12Q1/68 ,  C12N5/02 ,  C07H21/04 ,  C12N15/113 ,  C12N15/63

CPC分类号： C12N15/113 ,  C12N15/63 ,  C12N15/635 ,  C12N2310/141 ,  C12N2330/51

摘要： This invention generally relates to a design and method for developing novel anti-tumor/cancer drugs, vaccines and therapies, using microRNA (miRNA) and its shRNA homologues/derivatives. More particularly, the present invention relates to the use of a nucleic acid composition capable of expressing mir-302-like gene silencing effectors upon delivery into human cells and then silencing mir-302-targeted cell cycle regulators and oncogenes, resulting in an inhibitory effect on tumor/cancer cell growth and metastasis. Mir-302 is the most predominant miRNA found in human embryonic stem (hES) and induced pluripotent stem (iPS) cells, yet its function is unclear. The present invention establishes that in humans mir-302 concurrently suppressed both cyclin-E-CDK2 and cyclin-D-CDK4/6 pathways and eventually blocked over 70% of the G1-S transition. Simultaneously, mir-302 also silences BMI-1, a cancer stem cell marker, and subsequently promotes the tumor suppressor functions of p16Ink4a and p14/p19Arf in inhibiting CDK4/6-mediated cell proliferation. Therefore, the present invention for the first time reveals the tumor suppressor function of mir-302 in humans. This novel finding advances the design and method for developing new cancer drugs, vaccines and therapies directed against multiple kinds of human tumors and cancers, in particular including, but not limited, malignant skin, prostate, breast and liver cancers as well as various tumors.

摘要翻译： 本发明一般涉及使用微小RNA（miRNA）及其shRNA同源物/衍生物开发新的抗肿瘤/癌症药物，疫苗和疗法的设计和方法。 更具体地说，本发明涉及在递送至人细胞后能够表达mir-302样基因沉默效应物，然后使mir-302靶向的细胞周期调节因子和致癌基因沉默的核酸组合物的用途，从而产生抑制作用 对肿瘤/癌细胞的生长和转移。 Mir-302是人类胚胎干细胞（hES）和诱导多能干（iPS）细胞中最主要的miRNA，但其功能尚不清楚。 本发明确定人mir-302同时抑制细胞周期蛋白E-CDK2和细胞周期蛋白-D-CDK4 / 6途径，并最终阻断70％以上的G1-S转换。 同时，mir-302还沉默BMI-1，一种癌症干细胞标记物，随后促进p16Ink4a和p14 / p19Arf抑制CDK4 / 6介导的细胞增殖的肿瘤抑制功能。 因此，本发明首次揭示了人类mir-302的肿瘤抑制功能。 该新发现推进了针对多种人类肿瘤和癌症开发新的癌症药物，疫苗和疗法的设计和方法，特别是包括但不限于恶性皮肤，前列腺癌，乳腺癌和肝癌以及各种肿瘤。

公开(公告)号：US09399773B2

公开(公告)日：2016-07-26

申请号：US14142512

申请日：2013-12-27

申请人： Shi-Lung Lin ,  Donald Chang ,  David T S Wu

发明人： Shi-Lung Lin ,  Donald Chang ,  David T S Wu

IPC分类号： C12P19/34 ,  C12Q1/68 ,  C12N1/20 ,  C07H21/04 ,  C12N15/113 ,  C12N15/11

CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/141 ,  C12N2330/50 ,  C12N2330/51

摘要： This invention generally relates to a composition for developing novel anti-cancer drugs and/or vaccines and producing microRNA precursor (pre-miRNA) and/or its shRNA homologs/mimics/derivatives, and a method thereof. The present invention also relates to a use of a composition in producing novel prokaryote-produced microRNA precursor (pro-miRNA) capable of being delivered into human cells and processed by the cells into microRNA-like effectors to elicit specific silencing effects on certain targeted oncogenes, subsequently leading to a therapeutic result of tumor suppression and cancer therapy. Specifically, the method of the present invention includes inducing an expression of the pre-miRNA/pro-miRNAs, particularly human pre-miR-302, in prokaryotes through pol-2 or pol-2-like RNA promoter. Most importantly, the composition of the present invention is further a novel pre-miRNA-based drug that is capable of reprogramming the malignant properties of high-grade human liver cancers into a low-grade benign or even relatively normal stage—a mechanism called “Cancer Reversion”.

摘要翻译： 本发明一般涉及用于开发新型抗癌药物和/或疫苗并产生微小RNA前体（pre-miRNA）和/或其shRNA同源物/模拟物/衍生物的组合物及其方法。 本发明还涉及一种组合物在生产新型原核生产的微小RNA前体（pro-miRNA）中的用途，其能够被递送到人类细胞中并被细胞加工成微小RNA样效应物以引发对某些靶向癌基因的特异性沉默效应 ，随后导致肿瘤抑制和癌症治疗的治疗结果。 具体地说，本发明的方法包括通过pol-2或pol-2样RNA启动子在原核生物中诱导前miRNA /前miRNAs，特别是人pre-miR-302的表达。 最重要的是，本发明的组合物还是一种新的基于前体miRNA的药物，其能够将高级别人类肝癌的恶性特征重新编程成低级良性或甚至相对正常的阶段 - 称为“ 癌症逆转“。

公开(公告)号：US09387251B2

公开(公告)日：2016-07-12

申请号：US14457829

申请日：2014-08-12

申请人： Shi-Lung Lin ,  David T S Wu

发明人： Shi-Lung Lin ,  Yi-Wen Lin

IPC分类号： A61K47/26 ,  A61K31/713 ,  A61K31/7105 ,  C12N15/11 ,  C12N15/113

CPC分类号： A61K47/26 ,  A61K31/7105 ,  A61K31/713 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/141 ,  C12N2320/32 ,  C12N2330/50 ,  C12N2330/51 ,  C12N2740/15041

摘要： This invention relates to a composition and its use for formulating nucleic acid-based drugs/vaccines with sugar alcohol compositions into complexes for both in-vitro and in-vivo delivery. Particularly, the present invention includes the ingredients and processes necessary for formulating therapeutic and pharmaceutical nucleic acid compositions, such as miRNA, microRNA precursors, shRNAs, siRNAs, ribozymes, antisense RNAs/DNAs, RNA-DNA hybrids and DNA vectors/vaccines, with glycylated sugar alcohols/sugars into delivery complexes, which can then be absorbed by cells in vivo and in vitro via active endocytosis. Also, the present invention discloses that chemical compounds containing sugar alcohol- and/or sugar-like structures can protect nucleic acids, in particular miRNAs, shRNAs, siRNAs and ribozymes, from degradation in vivo as well as in vitro. Therefore, the present invention is also a formula and method for preserving the structural integrity and functional efficacy of these nucleic acid-based drugs and/or vaccines in vivo and in vitro.

摘要翻译： 本发明涉及一种组合物及其用于将糖醇组合物配制成用于体外和体内递送的复合物的基于核酸的药物/疫苗的用途。 特别地，本发明包括配制具有糖基化的治疗和药物核酸组合物如miRNA，微RNA前体，shRNA，siRNA，核酶，反义RNA / DNA，RNA-DNA杂交体和DNA载体/疫苗所必需的成分和方法 糖醇/糖进入递送复合物，其然后可以通过活性内吞作用在体内和体外被细胞吸收。 此外，本发明公开了含有糖醇和/或糖类结构的化合物可以保护核酸，特别是miRNA，shRNA，siRNA和核酶免受体内和体外降解。 因此，本发明也是用于在体内和体外保持这些基于核酸的药物和/或疫苗的结构完整性和功能功效的配方和方法。

公开(公告)号：US09422559B2

公开(公告)日：2016-08-23

申请号：US13964705

申请日：2013-08-12

申请人： Shi-Lung Lin ,  David T S Wu

发明人： Shi-Lung Lin ,  David T S Wu

IPC分类号： C12N15/11 ,  C12N15/00 ,  C07H21/02 ,  C12N15/113

CPC分类号： C12N15/1137 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/141 ,  C12N2330/50 ,  C12N2330/51

摘要： This invention generally relates to a design and method for developing novel anti-tumor and/or anti-cancer drugs, vaccines and therapies, using microRNA and/or its shRNA homologs/mimics/derivatives. More specifically, the present invention relates to an use of a prokaryote-produced miRNA precursor (pro-miRNA) composition capable of being delivered into human cells and processed by the cells into mature miRNA effectors to elicit specific silencing effects on mir-302-targeted genes, subsequently leading to a beneficial result of tumor suppression and cancer therapy. The prokaryotic cells do not naturally express or process eukaryotic miRNA precursors (pre-miRNA); meanwhile, the present invention also teaches an inducible method for expressing pre-miRNAs, particularly mir-302 precursors by using the prokaryotic transcription system. Since mir-302 is a known tumor suppressor in human, this novel finding advances the design and method for developing new anti-cancer drugs, vaccines and/or therapies directed against multiple kinds of human tumors and cancers.

摘要翻译： 本发明一般涉及使用微小RNA和/或其shRNA同源物/模拟物/衍生物开发新的抗肿瘤和/或抗癌药物，疫苗和疗法的设计和方法。 更具体地，本发明涉及能够被递送到人细胞中并由细胞加工成成熟miRNA受体的原核生产的miRNA前体（pro-miRNA）组合物的用途，以对mir-302靶向引发特异性沉默效应 基因，随后导致肿瘤抑制和癌症治疗的有益结果。 原核细胞不是天然表达或加工真核miRNA前体（pre-miRNA）; 同时，本发明还教导了通过使用原核转录系统表达前miRNAs，特别是mir-302前体的诱导型方法。 由于mir-302是人类已知的肿瘤抑制因子，因此该新发现推进了开发针对多种人类肿瘤和癌症的新的抗癌药物，疫苗和/或疗法的设计和方法。

公开(公告)号：US20130210120A1

公开(公告)日：2013-08-15

申请号：US13572263

申请日：2012-08-10

申请人： Shi-Lung Lin ,  Donald C. Chang

发明人： Shi-Lung Lin ,  Donald C. Chang

IPC分类号： C12N15/70

CPC分类号： C12N15/635 ,  C12N1/38 ,  C12N15/70

摘要： Eukaryotic protein-coding messenger RNAs and non-coding microRNAs are naturally transcribed by type II RNA polymerases (pol-2) but not prokaryotic RNA polymerases. As a result, current eukaryotic RNA and protein production is performed either using eukaryotic pol-2 promoters in hybridomas or mammalian cells or using prokaryotic promoters in bacterial cells. However, because prokaryotic RNA transcription tends to be error-prone, frequent mutation is a big problem. Also, growing hybridomas or mammalian cells is relatively laborious and costly. To overcome these problems, the present invention provides a novel inducible composition and method for producing eukaryotic RNAs and/or their related peptides/proteins directly using eukaryotic pol-2 promoter-driven gene expression in fast growing bacteria, without the need of changing to prokaryotic promoters or growing hybridomas/mammalian cells. The RNAs and peptides/proteins so obtained can be used to develop drugs, cure diseases, treat tumors/cancers, produce pluripotent stem (iPS) cells, enhance wound healing, and make foods.

摘要翻译： 真核生物蛋白质编码的信使RNA和非编码微小RNA由II型RNA聚合酶（pol-2）天然转录而不是原核RNA聚合酶。 结果是，目前的真核RNA和蛋白质生产在杂交瘤或哺乳动物细胞中使用真核的pol-2启动子，或者在细菌细胞中使用原核启动子。 然而，由于原核RNA转录往往容易出错，频繁突变是一个大问题。 此外，生长中的杂交瘤或哺乳动物细胞相对费力和费用高昂。 为了克服这些问题，本发明提供了一种用于在快速生长的细菌中直接使用真核的pol-2启动子驱动的基因表达来生产真核RNA和/或其相关肽/蛋白质的新型诱导组合物和方法，而不需要改变为原核生物 启动子或生长杂交瘤/哺乳动物细胞。 如此获得的RNA和肽/蛋白质可用于开发药物，治愈疾病，治疗肿瘤/癌症，产生多能干细胞（iPS）细胞，增强伤口愈合和制备食物。

公开(公告)号：US09453219B2

公开(公告)日：2016-09-27

申请号：US12003662

申请日：2007-12-28

申请人： Shi-Lung Lin ,  David TS Wu

发明人： Shi-Lung Lin ,  David TS Wu

IPC分类号： C12N15/113 ,  C12N15/11

CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N2310/111 ,  C12N2310/141 ,  C12N2320/30 ,  C12N2320/50

摘要： The present invention relates to a method and composition for generating a non-naturally occurring intron and its components capable of being processed into small hairpin RNA (shRNA) and/or microRNA (miRNA) molecules by skin cells and thus inducing specific gene silencing effects on skin pigment-related genes and/or aging-causing genes in the cells. The gene silencing effects so obtained are not only useful for lightening and whitening skin colors but also useful for suppressing unwanted aging gene activities in skins.

摘要翻译： 本发明涉及一种用于产生非天然存在的内含子及其组分的方法和组合物，其能够被皮肤细胞加工成小发夹RNA（shRNA）和/或微小RNA（miRNA）分子，从而诱导特定的基因沉默效应 皮肤色素相关基因和/或衰老基因。 如此获得的基因沉默效应不仅可用于减轻和增白皮肤颜色，还可用于抑制皮肤中不需要的老化基因活性。

公开(公告)号：US20150209377A1

公开(公告)日：2015-07-30

申请号：US14585978

申请日：2014-12-30

申请人： Shi-Lung Lin ,  Samantha Chang-Lin ,  Yi-Wen Lin ,  Donald Chang

发明人： Shi-Lung Lin ,  Samantha Chang-Lin ,  Yi-Wen Lin ,  Donald Chang

IPC分类号： A61K31/7012 ,  A61K31/221

CPC分类号： A61K31/221 ,  A61K9/0053 ,  A61K9/08 ,  A61K31/7012 ,  A61K31/7024 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/141 ,  C12N2320/32 ,  C12N2330/50 ,  C12N2330/51

摘要： This invention is related to a novel sugar-like chemical composition and its use for diabetes therapy. Particularly, the present invention teaches the use of monosaccharide-like glycylated sugar alcohol compounds to block or reduce sugar absorption in diabetes patients, so as to prevent the risk of hyperglycemia symptoms. Glycylation of sugar alcohols is a totally novel reaction that has never been reported before. Therefore, the novelty of the present invention is that for the first time glycylated sugar alcohols not only was found but also was found to be useful for treating Diabetes mellitus. In addition, the present invention teaches a method for producing these glycylated sugar alcohols. In sum, the present invention includes not only a kind of novel sugar-like chemical compositions and its use for treating diabetes but also a state-of-the-art protocol and methodology for producing such a novel composition via glycylation of sugars and sugar alcohols.

摘要翻译： 本发明涉及新型糖类化学组合物及其用于糖尿病治疗的用途。 特别地，本发明教导了使用单糖样的糖化糖醇化合物来阻止或减少糖尿病患者的糖吸收，以防止高血糖症状的风险。 糖醇的糖基化是一种完全新颖的反应，从未在之前报道过。 因此，本发明的新颖性不仅首次发现了糖化糖醇，而且被发现可用于治疗糖尿病。 此外，本发明教导了一种制备这些糖基化糖醇的方法。 总之，本发明不仅包括一种新型的糖类化学组合物及其用于治疗糖尿病的用途，而且还包括通过糖和糖醇的糖基化制备这种新型组合物的最新方案和方法 。