公开(公告)号：US09523101B2

公开(公告)日：2016-12-20

申请号：US14322097

申请日：2014-07-02

Applicant: The Catholic University of America

Inventor： Venigalla B. Rao

IPC: C12N15/86 ,  C12N15/87 ,  C07K14/005 ,  C12N7/00 ,  C12N15/88 ,  A61K47/48 ,  A61K31/7088 ,  A61K31/711 ,  A61K48/00

CPC classification number: C12N15/86 ,  A61K31/7088 ,  A61K31/711 ,  A61K47/48776 ,  A61K47/6901 ,  A61K48/00 ,  C07K14/005 ,  C12N7/00 ,  C12N15/87 ,  C12N15/88 ,  C12N2795/10042 ,  C12N2795/10122 ,  C12N2795/10142 ,  C12N2795/10152

Abstract: Complex viruses are assembled from simple protein subunits by sequential and irreversible assembly. During genome packaging in bacteriophages, a powerful molecular motor assembles at the special portal vertex of an empty prohead to initiate packaging. An aspect of the invention relates to the phage T4 packaging machine being highly promiscuous, translocating DNA into finished phage heads as well as into proheads. Single motors can force exogenous DNA into phage heads at the same rate as into proheads and phage heads undergo repeated initiations, packaging multiple DNA molecules into the same head. This shows that the phage DNA packaging machine has unusual conformational plasticity, powering DNA into an apparently passive capsid receptacle, including the highly stable virus shell, until it is full. These features allow for the design of a novel class of nanocapsid delivery vehicles.

公开(公告)号：US20140335158A1

公开(公告)日：2014-11-13

申请号：US14322097

申请日：2014-07-02

Applicant: The Catholic University of America

Inventor： Venigalla B. Rao

IPC: C12N15/86 ,  A61K47/48 ,  C12N7/00

CPC classification number: C12N15/86 ,  A61K31/7088 ,  A61K31/711 ,  A61K47/48776 ,  A61K47/6901 ,  A61K48/00 ,  C07K14/005 ,  C12N7/00 ,  C12N15/87 ,  C12N15/88 ,  C12N2795/10042 ,  C12N2795/10122 ,  C12N2795/10142 ,  C12N2795/10152

Abstract: Complex viruses are assembled from simple protein subunits by sequential and irreversible assembly. During genome packaging in bacteriophages, a powerful molecular motor assembles at the special portal vertex of an empty prohead to initiate packaging. An aspect of the invention relates to the phage T4 packaging machine being highly promiscuous, translocating DNA into finished phage heads as well as into proheads. Single motors can force exogenous DNA into phage heads at the same rate as into proheads and phage heads undergo repeated initiations, packaging multiple DNA molecules into the same head. This shows that the phage DNA packaging machine has unusual conformational plasticity, powering DNA into an apparently passive capsid receptacle, including the highly stable virus shell, until it is full. These features allow for the design of a novel class of nanocapsid delivery vehicles.

Abstract translation: 复杂病毒通过顺序和不可逆组装由简单蛋白质亚基组装。 在噬菌体的基因组包装过程中，一个强大的分子马达组装在一个空头颅的特殊门户顶点，开始包装。 本发明的一个方面涉及高度混杂的噬菌体T4包装机，将DNA转运到成品噬菌体头以及pro头中。 单个电机可以将外源DNA以与头孢子相同的速率强制进入噬菌体头，并且噬菌体头经历反复引发，将多个DNA分子包装在相同的头中。 这表明噬菌体DNA包装机具有不寻常的构象可塑性，将DNA提供到明显被动的衣壳容器中，包括高度稳定的病毒壳，直至其充满。 这些特征允许设计一种新型的纳米框输送车辆。

公开(公告)号：US10556002B2

公开(公告)日：2020-02-11

申请号：US15892772

申请日：2018-02-09

Applicant: The Catholic University of America

Inventor： Venigalla B. Rao

IPC: A61K39/295 ,  A61K39/385 ,  A61K39/07 ,  A61K39/02 ,  C07K14/24 ,  C07K14/32 ,  C07K14/005 ,  C07K19/00 ,  A61K39/00

Abstract: Bivalent immunogenic compositions against anthrax and plague are disclosed herein. One bivalent immunogenic composition comprises a triple fusion protein containing three antigens, F1 and V from Yersinia pestis and PA antigen from Bacillus anthracia fused in-frame and retaining structural and functional integrity of all three antigens. Another bivalent immunogenic composition comprises bacteriophage nanoparticles arrayed with these three antigens on the capsid surface of the bacteriophage nanoparticles. These bivalent immunogenic compositions are able to elicit robust immune response in a subject administered said the bivalent immunogenic compositions and provide protection to the subject against sequential or simultaneous challenge with both anthrax and plague pathogens.

公开(公告)号：US09834583B2

公开(公告)日：2017-12-05

申请号：US14806727

申请日：2015-07-23

Applicant: THE CATHOLIC UNIVERSITY OF AMERICA

Inventor： Venigalla B. Rao ,  Wadad Alsalmi

IPC: A61K39/21 ,  C07K14/005 ,  C12N7/00 ,  A61K9/70 ,  C07K1/22 ,  C07K1/36 ,  A61K39/12 ,  C07K14/16 ,  A61K39/00

CPC classification number: C07K14/005 ,  A61K9/7023 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/54 ,  A61K2039/627 ,  C07K1/22 ,  C07K1/36 ,  C07K14/162 ,  C07K2319/00 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/22 ,  C07K2319/40 ,  C07K2319/50 ,  C12N7/00 ,  C12N2740/16022 ,  C12N2740/16043 ,  C12N2740/16051 ,  C12N2740/16111 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234

Abstract: An approach of producing recombinant trimers that mimic native HIV-1 envelope trimers is developed. A recombinant protein forming the recombinant trimers encompasses a recombinant HIV-1 gp140 fused to a tag through a linker at C-terminus of the recombinant HIV-1 gp140. The linker is sufficiently long so that the tag is accessible for binding by a binding molecule bound on a solid matrix. After expressed in a cell, the recombinant protein is secreted into the culture medium and assembles into recombinant trimers therein. The recombinant trimers may be directly purified from the culture medium. Cleaved and uncleaved trimers from different clade viruses are produced.

公开(公告)号：US09580477B2

公开(公告)日：2017-02-28

申请号：US14806739

申请日：2015-07-23

Applicant: THE CATHOLIC UNIVERSITY OF AMERICA

Inventor： Venigalla B. Rao ,  Wadad Alsalmi

IPC: C12N15/00 ,  C07H21/04 ,  C07K14/005 ,  C12N7/00 ,  A61K9/70 ,  A61K39/21 ,  C07K1/22 ,  C07K1/36 ,  A61K39/12 ,  A61K39/00

CPC classification number: C07K14/005 ,  A61K9/7023 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/54 ,  A61K2039/627 ,  C07K1/22 ,  C07K1/36 ,  C07K14/162 ,  C07K2319/00 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/22 ,  C07K2319/40 ,  C07K2319/50 ,  C12N7/00 ,  C12N2740/16022 ,  C12N2740/16043 ,  C12N2740/16051 ,  C12N2740/16111 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234

Abstract: An approach of producing recombinant trimers that mimic native HIV-1 envelope trimers is developed. A recombinant protein forming the recombinant trimers encompasses a recombinant HIV-1 gp140 fused to a tag through a linker at C-terminus of the recombinant HIV-1 gp140. The linker is sufficiently long so that the tag is accessible for binding by a binding molecule bound on a solid matrix. After expressed in a cell, the recombinant protein is secreted into the culture medium and assembles into recombinant trimers therein. The recombinant trimers may be directly purified from the culture medium. Cleaved and uncleaved trimers from different clade viruses are produced.

Abstract translation: 开发了生产模仿天然HIV-1包膜三聚体的重组三聚体的方法。 形成重组三聚体的重组蛋白包含通过重组HIV-1 gp140的C-末端的接头与标签融合的重组HIV-1 gp140。 接头足够长，使得标签可通过结合在固体基质上的结合分子进行结合。 在细胞中表达后，将重组蛋白分泌到培养基中并在其中组装成重组三聚体。 重组三聚体可以从培养基中直接纯化。 产生来自不同进化枝病毒的切割和未切割的三聚体。

公开(公告)号：US09328145B2

公开(公告)日：2016-05-03

申请号：US14091401

申请日：2013-11-27

Applicant: The Catholic University of America

Inventor： Venigalla B. Rao ,  Guofen Gao

IPC: C07K14/005

CPC classification number: C07K14/005 ,  C07K2319/35 ,  C07K2319/70 ,  C07K2319/735 ,  C12N7/00 ,  C12N7/02 ,  C12N2740/16122 ,  C12N2740/16222 ,  C12N2795/10122 ,  C12N2795/10123

Abstract: Described herein is a soluble HIV-1 retrovirus transmembrane glycoprotein gp41 trimer (Soc-gp41M-Fd) containing a partial ectodomain and the cytoplasmic domain, that is fused to the small outer capsid (Soc) protein of bacteriophage T4 and the Foldon domain of the bacteriophage T4 fibritin (Fd). The gp41 trimer that has a prehairpin structure could be utilized to understand the mechanism of viral entry and as a candidate for development of HIV-1 vaccines, diagnostics and therapeutics. Other secondary embodiments of the gp41 proteins containing different modifications are also disclosed. According to one embodiment, the gp41 trimer is further attached to a cell penetration peptide (CPP). Methods of producing gp41 trimers are also disclosed.

Abstract translation: 本文描述的是含有部分胞外域和细胞质结构域的可溶性HIV-1逆转录病毒跨膜糖蛋白gp41三聚体（Soc-gp41M-Fd），其与噬菌体T4的小外壳（Soc）蛋白和 噬菌体T4纤维蛋白（Fd）。 具有前贴片结构的gp41三聚体可用于了解病毒进入的机制，并且作为HIV-1疫苗，诊断和治疗学的发展的候选者。 还公开了含有不同修饰物的gp41蛋白质的其它次要实施方案。 根据一个实施方案，gp41三聚体进一步连接于细胞穿透肽（CPP）。 还公开了生产gp41三聚体的方法。

公开(公告)号：US10005819B2

公开(公告)日：2018-06-26

申请号：US15817761

申请日：2017-11-20

Applicant: The Catholic University of America

Inventor： Venigalla B. Rao ,  Wadad Alsalmi

IPC: C07K14/005 ,  C12N7/00 ,  A61K39/12 ,  C07K1/36 ,  C07K1/22 ,  A61K39/21 ,  A61K9/70 ,  C07K14/16 ,  A61K39/00

CPC classification number: C07K14/005 ,  A61K9/7023 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/54 ,  A61K2039/627 ,  C07K1/22 ,  C07K1/36 ,  C07K14/162 ,  C07K2319/00 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/22 ,  C07K2319/40 ,  C07K2319/50 ,  C12N7/00 ,  C12N2740/16022 ,  C12N2740/16043 ,  C12N2740/16051 ,  C12N2740/16111 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234

Abstract: An approach of producing recombinant trimers that mimic native HIV-1 envelope trimers is developed. A recombinant protein forming the recombinant trimers encompasses a recombinant HIV-1 gp140 fused to a tag through a linker at C-terminus of the recombinant HIV-1 gp140. The linker is sufficiently long so that the tag is accessible for binding by a binding molecule bound on a solid matrix. After expressed in a cell, the recombinant protein is secreted into the culture medium and assembles into recombinant trimers therein. The recombinant trimers may be directly purified from the culture medium. Cleaved and uncleaved trimers from different clade viruses are produced.

公开(公告)号：US09975924B2

公开(公告)日：2018-05-22

申请号：US14806742

申请日：2015-07-23

Applicant: THE CATHOLIC UNIVERSITY OF AMERICA

Inventor： Venigalla B. Rao ,  Wadad Alsalmi

IPC: C07K14/005 ,  C12N7/00 ,  A61K9/70 ,  A61K39/21 ,  C07K1/22 ,  C07K1/36 ,  A61K39/12 ,  C07K14/16 ,  A61K39/00

CPC classification number: C07K14/005 ,  A61K9/7023 ,  A61K39/00 ,  A61K39/12 ,  A61K39/21 ,  A61K2039/54 ,  A61K2039/627 ,  C07K1/22 ,  C07K1/36 ,  C07K14/162 ,  C07K2319/00 ,  C07K2319/20 ,  C07K2319/21 ,  C07K2319/22 ,  C07K2319/40 ,  C07K2319/50 ,  C12N7/00 ,  C12N2740/16022 ,  C12N2740/16043 ,  C12N2740/16051 ,  C12N2740/16111 ,  C12N2740/16122 ,  C12N2740/16134 ,  C12N2740/16234

Abstract: An approach of producing recombinant trimers that mimic native HIV-1 envelope trimers is developed. A recombinant protein forming the recombinant trimers encompasses a recombinant HIV-1 gp140 fused to a tag through a linker at C-terminus of the recombinant HIV-1 gp140. The linker is sufficiently long so that the tag is accessible for binding by a binding molecule bound on a solid matrix. After expressed in a cell, the recombinant protein is secreted into the culture medium and assembles into recombinant trimers therein. The recombinant trimers may be directly purified from the culture medium. Cleaved and uncleaved trimers from different clade viruses are produced.

公开(公告)号：US09701722B2

公开(公告)日：2017-07-11

申请号：US15080804

申请日：2016-03-25

Applicant: The Catholic University of America

Inventor： Venigalla B. Rao ,  Guofen Gao

IPC: C07K14/05 ,  C07K14/005 ,  C12N7/02 ,  C12N7/00

CPC classification number: C07K14/005 ,  C07K2319/35 ,  C07K2319/70 ,  C07K2319/735 ,  C12N7/00 ,  C12N7/02 ,  C12N2740/16122 ,  C12N2740/16222 ,  C12N2795/10122 ,  C12N2795/10123

Abstract: Described herein is a soluble HIV-1 retrovirus transmembrane glycoprotein gp41 trimer (Soc-gp41M-Fd) containing a partial ectodomain and the cytoplasmic domain, that is fused to the small outer capsid (Soc) protein of bacteriophage T4 and the Foldon domain of the bacteriophage T4 fibritin (Fd). The gp41 trimer that has a prehairpin structure could be utilized to understand the mechanism of viral entry and as a candidate for development of HIV-1 vaccines, diagnostics and therapeutics. Other secondary embodiments of the gp41 proteins containing different modifications are also disclosed. According to one embodiment, the gp41 trimer is further attached to a cell penetration peptide (CPP). Methods of producing gp41 trimers are also disclosed.

公开(公告)号：US09365867B2

公开(公告)日：2016-06-14

申请号：US13796263

申请日：2013-03-12

Applicant: THE CATHOLIC UNIVERSITY OF AMERICA

Inventor： Venigalla B. Rao

IPC: C12N7/00 ,  C12N15/86 ,  A61K31/7088 ,  A61K31/711 ,  C12N15/87 ,  C12N15/88 ,  C07K14/005 ,  A61K47/48 ,  A61K48/00

CPC classification number: C12N15/86 ,  A61K31/7088 ,  A61K31/711 ,  A61K47/48776 ,  A61K47/6901 ,  A61K48/00 ,  C07K14/005 ,  C12N7/00 ,  C12N15/87 ,  C12N15/88 ,  C12N2795/10042 ,  C12N2795/10122 ,  C12N2795/10142 ,  C12N2795/10152

Abstract: Complex viruses are assembled from simple protein subunits by sequential and irreversible assembly. During genome packaging in bacteriophages, a powerful molecular motor assembles at the special portal vertex of an empty prohead to initiate packaging. An aspect of the invention relates to the phage T4 packaging machine being highly promiscuous, translocating DNA into finished phage heads as well as into proheads. Single motors can force exogenous DNA into phage heads at the same rate as into proheads and phage heads undergo repeated initiations, packaging multiple DNA molecules into the same head. This shows that the phage DNA packaging machine has unusual conformational plasticity, powering DNA into an apparently passive capsid receptacle, including the highly stable virus shell, until it is full. These features allow for the design of a novel class of nanocapsid delivery vehicles.

Abstract translation: 复杂病毒通过顺序和不可逆组装由简单蛋白质亚基组装。 在噬菌体的基因组包装过程中，一个强大的分子马达组装在一个空头颅的特殊门户顶点，开始包装。 本发明的一个方面涉及高度混杂的噬菌体T4包装机，将DNA转运到成品噬菌体头以及pro头中。 单个电机可以将外源DNA以与头孢子相同的速率强制进入噬菌体头，并且噬菌体头经历反复引发，将多个DNA分子包装在相同的头中。 这表明噬菌体DNA包装机具有不寻常的构象可塑性，将DNA提供到明显被动的衣壳容器中，包括高度稳定的病毒壳，直至其充满。 这些特征允许设计一种新型的纳米框输送车辆。