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  • 1
    Online Resource
    Online Resource
    Publisher Correction: A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity
    Springer Science and Business Media LLC ; 2021
    In:  Nature Vol. 590, No. 7844 ( 2021-02-04), p. E23-E23
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 590, No. 7844 ( 2021-02-04), p. E23-E23
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-020-03108-4
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
    SSG: 11
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  • 2
    Online Resource
    Online Resource
    Targeting tumor vasculature endothelial cells and tumor cells for immunotherapy of human melanoma in a mouse xenograft model
    Proceedings of the National Academy of Sciences ; 1999
    In:  Proceedings of the National Academy of Sciences Vol. 96, No. 14 ( 1999-07-06), p. 8161-8166
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 96, No. 14 ( 1999-07-06), p. 8161-8166
    Abstract: An immunotherapy treatment for cancer that targets both the tumor vasculature and tumor cells has shown promising results in a severe combined immunodeficient mouse xenograft model of human melanoma. The treatment involves systemic delivery of an immunoconjugate molecule composed of a tumor-targeting domain conjugated to the Fc effector domain of human IgG1. The effector domain induces a cytolytic immune response against the targeted cells by natural killer cells and complement. Two types of targeting domains were used. One targeting domain is a human single-chain Fv molecule that binds to a chondroitin sulfate proteoglycan expressed on the surface of most human melanoma cells. Another targeting domain is factor VII (fVII), a zymogen that binds with high specificity and affinity to the transmembrane receptor tissue factor (TF) to initiate the blood coagulation cascade. TF is expressed by endothelial cells lining the tumor vasculature but not the normal vasculature, and also by many types of tumor cells including melanoma. Because the binding of a fVII immunoconjugate to TF might cause disseminated intravascular coagulation, the active site of fVII was mutated to inhibit coagulation without affecting the affinity for TF. The immunoconjugates were encoded as secreted molecules in a replication-defective adenovirus vector, which was injected into the tail vein of severe combined immunodeficient mice. The results demonstrate that a mutated fVII immunoconjugate, administered separately or together with a single-chain Fv immunoconjugate that binds to the tumor cells, can inhibit the growth or cause regression of an established human tumor xenograft. This procedure could be effective in treating a broad spectrum of human solid tumors that express TF on vascular endothelial cells and tumor cells.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.96.14.8161
    RVK:
    TA 1000
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1999
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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  • 3
    Online Resource
    Online Resource
    Retroviral-mediated transmission of a mouse VL30 RNA to human melanoma cells promotes metastasis in an immunodeficient mouse model
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 9 ( 2002-04-30), p. 6269-6273
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 9 ( 2002-04-30), p. 6269-6273
    Abstract: Infection of a human melanoma cell line by a retroviral vector resulted in transmission of a mouse VL30 (mVL30-1) retroelement RNA to some of the cells infected by the retrovirus, followed by synthesis, integration, and expression of the mVL30-1 cDNA. One vector carried a tissue factor (TF) transgene that generated high TF melanoma clones, and another vector was a control without the TF transgene that generated low TF clones. Some high TF melanoma clones contained the mVL30-1 retroelement and others did not, and some low TF melanoma clones contained the mVL30-1 retroelement and others did not. Each type of melanoma clone was tested for its metastatic potential in severe combined immunodeficient (SCID) mice, by i.v. injection of the cells to generate lung tumors. None of the low TF clones that either contained or lacked the mVL30-1 retroelement generated lung tumors, consistent with earlier results showing that high TF expression promoted metastasis. The high TF clones containing the mVL30-1 retroelement were strongly metastatic, in contrast to the high TF clones lacking the mVL30-1 retroelement, which were weakly metastatic. Southern hybridization analyses showed that the mVL30-1 cDNA integrated into different genomic sites in different melanoma clones, suggesting that the effect of the mVL30-1 retroelement on metastasis depends not on integration per se but instead on expression of the mVL30-1 RNA. A role for the mVL30-1 RNA in metastasis and possibly other cell functions is an unexpected finding, because the RNA appears to lack significant coding potential for a functional protein. The metastatic effect might be mediated directly by a noncoding mVL30-1 RNA or by a peptide or small protein encoded by one of the short ORFs in the mVL30-1 RNA.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.092112199
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity
    Springer Science and Business Media LLC ; 2020
    In:  Nature Vol. 586, No. 7830 ( 2020-10-22), p. 572-577
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 586, No. 7830 ( 2020-10-22), p. 572-577
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/s41586-020-2599-8
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
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  • 5
    Online Resource
    Online Resource
    Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 5 ( 2003-03-04), p. 2679-2684
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 5 ( 2003-03-04), p. 2679-2684
    Abstract: Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0438014100
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Engineering carboxylic acid reductase for selective synthesis of medium-chain fatty alcohols in yeast
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 37 ( 2020-09-15), p. 22974-22983
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 37 ( 2020-09-15), p. 22974-22983
    Abstract: Medium-chain fatty alcohols (MCFOHs, C6 to C12) are potential substitutes for fossil fuels, such as diesel and jet fuels, and have wide applications in various manufacturing processes. While today MCFOHs are mainly sourced from petrochemicals or plant oils, microbial biosynthesis represents a scalable, reliable, and sustainable alternative. Here, we aim to establish a Saccharomyces cerevisiae platform capable of selectively producing MCFOHs. This was enabled by tailoring the properties of a bacterial carboxylic acid reductase from Mycobacterium marinum (MmCAR). Extensive protein engineering, including directed evolution, structure-guided semirational design, and rational design, was implemented. MmCAR variants with enhanced activity were identified using a growth-coupled high-throughput screening assay relying on the detoxification of the enzyme’s substrate, medium-chain fatty acids (MCFAs). Detailed characterization demonstrated that both the specificity and catalytic activity of MmCAR was successfully improved and a yeast strain harboring the best MmCAR variant generated 2.8-fold more MCFOHs than the strain expressing the unmodified enzyme. Through deletion of the native MCFA exporter gene TPO1 , MCFOH production was further improved, resulting in a titer of 252 mg/L for the final strain, which represents a significant improvement in MCFOH production in minimal medium by S. cerevisiae .
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2010521117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Targeting tissue factor on tumor vascular endothelial cells and tumor cells for immunotherapy in mouse models of prostatic cancer
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 21 ( 2001-10-09), p. 12180-12185
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 21 ( 2001-10-09), p. 12180-12185
    Abstract: The efficacy and safety of an immunoconjugate (icon) molecule, composed of a mutated mouse factor VII (mfVII) targeting domain and the Fc effector domain of an IgG1 Ig (mfVII/Fc icon), was tested with a severe combined immunodeficient (SCID) mouse model of human prostatic cancer and an immunocompetent mouse model of mouse prostatic cancer. The SCID mice were first injected s.c. with a human prostatic tumor line, forming a skin tumor that produces a high blood titer of prostate-specific antigen and metastasizes to bone. The icon was encoded in a replication-incompetent adenoviral vector that was injected directly into the skin tumor. The tumor cells infected by the vector synthesize and secrete the icon into the blood, and the blood-borne icon binds with high affinity and specificity to mouse tissue factor expressed on endothelial cells lining the lumen of the tumor vasculature and to human tissue factor expressed on the tumor cells. The Fc domain of the icon activates a cytolytic immune attack against cells that bind the icon. The immunotherapy tests in SCID mice demonstrated that intratumoral injections of the adenoviral vector encoding the mfVII/human Fc icon resulted in long-term regression of the injected human prostatic tumor and also of a distant uninjected tumor, without associated toxicity to the mice. Comparable results were obtained with a SCID mouse model of human melanoma. At the end of the experiments the mice appeared to be free of viable tumor cells. This protocol also could be efficacious for treating cancer patients who have vascularized tumors.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.201420298
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 8
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    Online Resource
    Intratumoral injection of adenoviral vectors encoding tumor-targeted immunoconjugates for cancer immunotherapy
    Proceedings of the National Academy of Sciences ; 2000
    In:  Proceedings of the National Academy of Sciences Vol. 97, No. 16 ( 2000-08), p. 9221-9225
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 16 ( 2000-08), p. 9221-9225
    Abstract: The efficacy and safety of a new immunotherapy protocol for cancer were tested in a severe combined immunodeficient mouse model of human skin and metastatic lung melanoma. The protocol involves intratumoral injections of replication-incompetent adenoviral vectors encoding immunoconjugates composed of the Fc region of an IgG1 immunoglobulin conjugated to a tumor-targeting domain. One targeting domain is factor VII that binds to tissue factor expressed on endothelial cells lining the tumor neovasculature and on tumor cells; the active site of factor VII was mutated to inhibit the initiation of blood coagulation. Another targeting domain is a single-chain Fv antibody that binds to a cognate antigen expressed on human melanoma cells. The adenoviral vectors infect mainly the cells of the injected tumor, which synthesize and secrete the immunoconjugates. The bloodborne immunoconjugates induce a cytolytic immune response against the targeted neovasculature endothelial cells and tumor cells. The mouse model experiments showed that intratumoral delivery of the factor VII immunoconjugate, either alone or together with the single-chain Fv immunoconjugate, resulted in growth inhibition and regression of the injected tumor, and also of distant metastatic tumors, without evidence of damage to normal organs. There was extensive destruction of the tumor neovasculature, presumably mediated by the factor VII immunoconjugate bound to tissue factor on neovasculature endothelial cells. Because tissue factor is generally expressed on neovascular endothelial cells and tumor cells, a factor VII immunoconjugate could be used for immunotherapy against a broad range of human solid tumors.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.97.16.9221
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2000
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
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    Crystal Structure of NLRC4 Reveals Its Autoinhibition Mechanism
    American Association for the Advancement of Science (AAAS) ; 2013
    In:  Science Vol. 341, No. 6142 ( 2013-07-12), p. 172-175
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 341, No. 6142 ( 2013-07-12), p. 172-175
    Abstract: Nucleotide-binding and oligomerization domain–like receptor (NLR) proteins oligomerize into multiprotein complexes termed inflammasomes when activated. Their autoinhibition mechanism remains poorly defined. Here, we report the crystal structure of mouse NLRC4 in a closed form. The adenosine diphosphate–mediated interaction between the central nucleotide-binding domain (NBD) and the winged-helix domain (WHD) was critical for stabilizing the closed conformation of NLRC4. The helical domain HD2 repressively contacted a conserved and functionally important α-helix of the NBD. The C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. Disruption of ADP-mediated NBD-WHD or NBD-HD2/NBD-LRR interactions resulted in constitutive activation of NLRC4. Together, our data reveal the NBD-organized cooperative autoinhibition mechanism of NLRC4 and provide insight into its activation.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1236381
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2013
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 10
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    Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis
    American Association for the Advancement of Science (AAAS) ; 2018
    In:  Science Vol. 361, No. 6403 ( 2018-08-17), p. 668-672
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 361, No. 6403 ( 2018-08-17), p. 668-672
    Abstract: With the recent soaring production of natural gas, the use of methane and other light hydrocarbon feedstocks as starting materials in synthetic transformations is becoming increasingly economically attractive, although it remains chemically challenging. We report the development of photocatalytic C–H amination, alkylation, and arylation of methane, ethane, and higher alkanes under visible light irradiation at ambient temperature. High catalytic efficiency (turnover numbers up to 2900 for methane and 9700 for ethane) and selectivity were achieved using abundant, inexpensive cerium salts as photocatalysts. Ligand-to-metal charge transfer excitation generated alkoxy radicals from simple alcohols that in turn acted as hydrogen atom transfer catalysts. The mixed-phase gas/liquid reaction was adapted to continuous flow, enabling the efficient use of gaseous feedstocks in scalable photocatalytic transformations.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aat9750
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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