Search

Your search keyword '"Zolotukhin AS"' showing total 4,959 results
Start Over Author "Zolotukhin AS"
4,959 results on '"Zolotukhin AS"'

201. INTRA-SPECIES GROUPINGS OF CHUM SALMON ONCORHYNCHUS KETA (SALMONIDAE) OF THE AMUR RIVER AND THEIR DISTRIBUTION WITHIN THE BASIN

Author

S. F. Zolotukhin

Subjects
amur river, chum salmon, intra-species grouping, population, spawning grounds, type of water supply, spawning redd, Aquaculture. Fisheries. Angling, SH1-691
Abstract

Chum salmon in the Amur River basin are represented by two races: summer and fall ones. For the summer race, one population with specific type of spawning grounds is known, but the fall race includes three populations with different types of spawning grounds. In total, four eco-geographical groupings of the species are separated in their reproduction by geographical boundaries of geomorphological zones, as well as temporally and ecologically. Chum salmon do not spawn in the Chinese part of the Amur basin in more than 50 years. In the Russian part, the summer chum salmon spawn completely in the hyporheic waters in late July — August, the major grouping of fall chum (77.1 %) spawns in the spring waters in September-November, other two groupings spawn in the hyporheic waters of the lower Amur in September (20.4 %) and in the spring waters of the lakes near the Amur mouth in October-November (2.5 %).

Published
2019
Full Text
View/download PDF

202. An Analysis of the Liver Transplant Waiting List at the G. G. Kuvatov Republican Clinical Hospital

Author

M. A. Nartailakov, R. R. Abdeev, I. Z. Salimgareev, A. R. Zagitov, R. R. Nuriakhmetov, I. I. Ivanov, K. N. Zolotukhin, I. V. Polyakov, and L. I. Bashirova

Subjects
печени трансплантация, лист ожидания, цирроз печени, эхинококкоз печени, печеночная недостаточность, безрецидивная выживаемость, прогноз, Surgery, RD1-811, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction. Liver transplantation is currently considered to be the only method of radical treatment for adults and children with incurable liver diseases. The most important aspects of liver transplantation are the correct selection of an appropriate recipient and compilation and maintenance of a liver transplant waiting list. This article aims to analyze the structure of the severe chronic liver disease patient population included in the liver transplant waiting list at the G. G. Kuvatov Republican Clinical Hospital (the City of Ufa).Materials and methods. We analyzed the waiting list drawn and maintained over the 2007-2018 period based on the examination of 789 patients with liver cirrhosis of various etiologies.Results and discussion. Out of all the patients with liver cirrhosis of different etiologies (Child-Pugh score classes A, B, and C) 149 (18.8 %) were included in the waiting list. The ages of patients included in the liver transplant waiting list ranged from 19 to 69. The mortality rate amounted to 38.9 % (58 people); of these patients 31 (53.4 %) had hepatic cirrhosis (HC) of autoimmune etiology, 18 (31.0 %) — HC of viral etiology, and 6 (10.3 %) — alveococcosis of the liver. The rate of the waiting list expansion for patients aged 20-29 compared to those aged 0-19 amounted to 1.32 %. Such a dynamics for the 30-39 age group compared to the 20-29 age group was 11.51 %. The number of people aged 40-49 compared to the preceding age group remained the same.Conclusion. Our analysis of the waiting list sets the percentage of patients with autoimmune HC in the population of patients with this disease at 59 %. These patients are characterized by a rapid progression of liver failure and high mortality. The statistical analysis of liver transplant waiting lists facilitate the optimization of procedures used to select and manage such patients, as well as to prevent, in a timely manner, the development of complications thus improving the prognosis of survival.

Published
2019
Full Text
View/download PDF

204. Middleware for Data Visualization in VO-enabled Data Archives

Author

Zolotukhin, Ivan and Chilingarian, Igor

Subjects
Astrophysics
Abstract

We present a middleware for visualization and exploration of complex datasets in a VO framework, that performs interaction between data archives and existing VO client applications using PLASTIC. It comprises: (1) PLASTIC-enabled Java control applet, integrated into archive web-pages and interacting with VO applications; (2) cross-browser compatible JavaScript part managing PLASTIC-aware VO Clients (launch, data manipulation) by means of Java LiveConnect. This (or similar) solution is an essential for the new generation VO-enabled data archives providing access to complex observational and theoretical datasets (3D-spectroscopy, N-body simulations, etc.) through web-interface. Thanks to PLASTIC capabilities it is possible to start all necessary client software with a single-click in the archive query result page in a web-browser. This simplifies the scientific usage of the VO resources and makes it easy even for users with no experience in the VO technologies., Comment: 4 pages, 1 figure, to appear in the proceedings of ADASS-XVII (ASP Conf. Series)

Published
2007

205. Visualization of Complex Observational and Theoretical Datasets in the Virtual Observatory

Author

Chilingarian, Igor and Zolotukhin, Ivan

Subjects
Astrophysics
Abstract

Our presentation is aimed at data centers providing access to complex observational and theoretical data and to the users of these resources. We show how to visualize complex datasets stored in the VO enabled data archives using existing VO client software and PLASTIC, a prototype of an application messaging protocol, for interaction between archive query results and tools. We demonstrate how to display and explore observable IFU datasets, provided within the ASPID-SR archive, using CDS Aladin, ESA VOSpec, and VO-Paris Euro3D Client. In the second part of the paper we show how to use TOPCAT for displaying results of N-body simulations of galaxy mergers available in the HORIZON GalMer database., Comment: 4 pages, 2 figures, to appear in the proceedings of ADASS-XVII (ASP Conf. Series)

Published
2007

206. 3D Spectroscopy in the Virtual Observatory: Current Status

Author

Chilingarian, Igor, Bonnarel, Francois, Louys, Mireille, Zolotukhin, Ivan, Royer, Frederic, Jegouzo, Isabelle, Sidaner, Pierre Le, Fernique, Pierre, and Boch, Thomas

Subjects
Astrophysics
Abstract

Three cornerstones for the 3D data support in the Virtual Observatory are: (1) data model to describe them, (2) data access services providing access to fully-reduced datasets, and (3) client applications which can deal with 3D data. Presently all these components became available in the VO. We demonstrate an application of the IVOA Characterisation data model to description of IFU and Fabry-Perot datasets. Two services providing SSA-like access to 3D-spectral data and Characterisation metadata have been implemented by us: ASPID-SR at SAO RAS for accessing IFU and Fabry-Perot data from the Russian 6-m telescope, and the Giraffe Archive at the VO Paris portal for the VLT FLAMES-Giraffe datasets. We have implemented VO Paris Euro3D Client, handling Euro3D FITS format, that interacts with CDS Aladin and ESA VOSpec using PLASTIC to display spatial and spectral cutouts of 3D datasets. Though the prototype we are presenting is yet rather simple, it demonstrates how 3D spectroscopic data can be fully integrated into the VO infrastructure., Comment: 4 pages, 1 figure. To appear in the proceedings of the ESA Workshop "Astronomical Spectroscopy and the Virtual Observatory" held in Villafranca del Castillo, Spain, in March 2007

Published
2007

207. Comprehensive Metadata Query Interface for Heterogeneous Data Archives Based on Open Source PostgreSQL ORDBMS

Author

Zolotukhin, Ivan, Samokhvalov, Nikolay, Bonnarel, Francois, and Chilingarian, Igor

Subjects
Astrophysics
Abstract

We use PostgreSQL DBMS for storing XML metadata, described by the IVOA Characterisation Data Model. Initial XML type support in the PostgreSQL has recently been implemented. We make heavy use of this feature in order to provide comprehensive search over Characterisation metadata tree. We built a prototype of the Characterisation metadata query service, implementing two access methods: (1) HTTP-GET/POST based interface implements almost direct translation of the query parameter name into XPath of the data model element in the XML serialisation; (2) Web-Service based interface to receive XQuery which is also directly translated into XPath. This service will be used in the ASPID-SR archive, containing science-ready data obtained with the Russian 6-m telescope., Comment: 3 pages, 1 figure. Proceedings of ADASS-XVI held in Tucson, AZ, USA, Oct.2006. To appear in the ASP Conference Series

Published
2007

208. ASPID-SR: Prototype of a VO-compliant Science-Ready Data Archive

Author

Chilingarian, Igor, Afanasiev, Victor, Bonnarel, Francois, Dodonov, Serguei, Louys, Mireille, and Zolotukhin, Ivan

Subjects
Astrophysics
Abstract

ASPID stands for the "Archive of Spectral, Photometric, and Interferometric Data". The world largest collection of raw 3D spectroscopic observations of galactic and extragalactic sources is provided. ASPID-SR is a prototype of an archive of heterogeneous science ready data, fed by ASPID, where we try to exploit all the power of the IVOA Characterisation Data Model. Multi-level Characterisation metadata is provided for every dataset. The archive provides powerful metadata query mechanism with access to every data model element, vital for the efficient scientific usage of a complex informational system. We provide a set of access interfaces: SIAP/SSAP, HTTP-based characterisation metadata query, Web-service accepting ADQL/x., Comment: 3 pages, no figures. Proceedings of ADASS-XVI held in Tucson, AZ, USA, Oct.2006. To appear in the ASP Conference Series. Formal presentation of the ASPID-SR archive (http://alcor.sao.ru/php/aspid-sr/)

Published
2007

209. Automated search for galactic star clusters in large multiband surveys: I. Discovery of 15 new open clusters in the Galactic anticenter region

Author

Koposov, S. E., Glushkova, E. V., and Zolotukhin, I. Yu.

Subjects
Astrophysics
Abstract

Aims: According to some estimations, there are as many as 100000 open clusters in the Galaxy, but less than 2000 of them have been discovered, measured, and cataloged. We plan to undertake data mining of multiwavelength surveys to find new star clusters. Methods: We have developed a new method to search automatically for star clusters in very large stellar catalogs, which is based on convolution with density functions. We have applied this method to a subset of the Two Micron All Sky Survey catalog toward the Galactic anticenter. We also developed a method to verify whether detected stellar groups are real star clusters, which tests whether the stars that form the spatial density peak also fall onto a single isochrone in the color-magnitude diagram. By fitting an isochrone to the data, we estimate at the same time the main physical parameters of a cluster: age, distance, color excess. Results: For the present paper, we carried out a detailed analysis of 88 overdensity peaks detected in a field of $16\times16$ degrees near the Galactic anticenter. From this analysis, 15 overdensities were confirmed to be new open clusters and the physical and structural parameters were determined for 12 of them; 10 of them were previously suspected to be open clusters by Kronberger (2006) and Froebrich (2007). The properties were also determined for 13 yet-unstudied known open clusters, thus almost tripling the sample of open clusters with studied parameters in the anticenter. The parameters determined with this method showed a good agreement with published data for a set of well-known clusters., Comment: accepted to A&A

Published
2007
Full Text
View/download PDF

210. Septic shock in obstetrics: guidelines of the All-Russian public organization 'Federation of Anesthesiologists and Reanimatologists'

Author

Alexander V. Kulikov, E. M. Shifman, D. N. Protsenko, A. M. Ovezov, Yu. S. Raspopin, N. V. Artymuk, T. E. Belokrynitskaya, K. N. Zolotukhin, A. V. Shchegolev, V. V. Kovalev, A. A. Matkovsky, D. O. Osipchuk, N. Yu. Pylaeva, O. V. Ryazanova, and I. B. Zabolotskikh

Subjects
Anesthesiology and Pain Medicine, Emergency Medicine, Critical Care and Intensive Care Medicine, Law
Abstract

The article reflects the main provisions of the clinical guidelines on septic shock in obstetrics, approved by the All-Russian public organization “Federation of Anesthesiologists-Resuscitators” in 2022. The relevance of the problem is associated with high mortality and morbidity rates from sepsis and septic shock in obstetrics. The main issues of etiology, pathogenesis, clinical picture, methods of laboratory and instrumental diagnostics, features of using the qSOFA, SOFA, MOEWS, SOS, MEWC, IMEWS scales for sepsis verification are consistently presented. The article presents the starting intensive therapy (the first 6–12 hours) of the treatment of septic shock in obstetrics, taking into account the characteristics of the pregnant woman's body. The strategy of prescribing vasopressors (norepinephrine, phenylephrine, epinephrine), inotropic drugs (dobutamine) is described, antibiotics and optimal antibiotic therapy regimens, features of infusion and adjuvant therapy are presented. The issues of surgical treatment of the focus of infection and indications for hysterectomy, as well as the organization of medical care and rehabilitation of patients with sepsis and septic shock were discussed. The basic principles of prevention of sepsis and septic shock in obstetrics are described. The criteria for the quality of medical care for patients with septic shock and the algorithms of doctor's actions in the diagnosis and intensive care of patients with septic shock in obstetrics are presented.

Published
2023
Full Text
View/download PDF

211. Direct Endolymphatic Ozone Therapy in Patients with Diabetic Foot Syndrome: Analysis of the Effectiveness

Author

Oleg Vladimirovich Zolotukhin, Maria Valerievna Аralova, Alexander Anatolyevich Glukhov, and Yuliya Nikolaevna Аlimkina

Subjects
Automotive Engineering
Abstract

Introduction. Chronic inflammatory process on the foot leads to the depletion of immune defense mechanisms against infection in patients with diabetes mellitus. Application of ozonized solutions, endolymphatic therapy contributes to fight against the infectious process and maintenance of the body homeostasis.The aim of the study was to evaluate safety and clinical effectiveness of direct endolymphatic ozone therapy in patients with purulent-necrotic complications of diabetic foot syndrome.Methods. Clinical outcomes of direct endolymphatic ozone therapy, being part of complex therapy, were analyzed in 23 patients with purulent-necrotic complications of diabetic foot syndrome. Inclusion criteria were the degree of damage to the foot according to Wagner 2-4, ankle-brachial index (ABI) less than 0.7. Direct antegrade endolymphatic ozone therapy consisted of introduction of ozonized isotonic sterile sodium chloride solution into the lymphatic collector of the middle third leg for 5 days. The parameters of treatment duration, degree of the pain syndrome, severity of surgical intervention, dynamics of the bacterial contamination, leukocytes and blood lymphocytes, leukocyte indices were assessed.Results. Under endolymphatic ozone therapy, all patients reported positive changes in subjective perception, the level of peripheral blood lymphocytes increased by 15.3%, which reflected an improvement in the adaptive potential of the body, bacterial contamination decreased by 68.6%, the severity of operations decreased by 39.4%. The duration of treatment did not change statistically significant. Conclusion. Direct endolymphatic ozone therapy is an effective way to influence the course of the purulent-necrotic process in the complex treatment of diabetic syndrome. The main focus of the technique is correction of the bacterial contamination of inflammation; this option promotes activation of reparative processes in the wound, reduces the risk of infection generalization, and preserves a limb footing ability. The use of leukocyte indices to assess the course of the inflammatory process on the foot in patients with diabetes mellitus is difficult in clinical practice due to the decreased body's reactivity.

Published
2023
Full Text
View/download PDF

212. Effect of CpG Depletion of Vector Genome on CD8+ T Cell Responses in AAV Gene Therapy

Author

Thais B. Bertolini, Jamie L. Shirley, Irene Zolotukhin, Xin Li, Tsuneyasu Kaisho, Weidong Xiao, Sandeep R. P. Kumar, and Roland W. Herzog

Subjects
CD8+ T cell, dendritic cells, CpG, adeno-associated virus, TLR9, gene therapy, Immunologic diseases. Allergy, RC581-607
Abstract

Adeno associated viral (AAV) vectors have emerged as a preferred platform for in vivo gene replacement therapy and represent one of the most promising strategies to treat monogenetic disorders such as hemophilia. However, immune responses to gene transfer have hampered human gene therapy in clinical trials. Over the past decade, it has become clear that innate immune recognition provides signals for the induction of antigen-specific responses against vector or transgene product. In particular, TLR9 recognition of the vector’s DNA genome in plasmacytoid dendritic cells (pDCs) has been identified as a key factor. Data from clinical trials and pre-clinical studies implement CpG motifs in the vector genome as drivers of immune responses, especially of CD8+ T cell activation. Here, we demonstrate that cross-priming of AAV capsid-specific CD8+ T cells depends on XCR1+ dendritic cells (which are likely the main cross-presenting cell that cooperates with pDCs to activate CD8+ T cells) and can be minimized by the elimination of CpG motifs in the vector genome. Further, a CpG-depleted vector expressing human coagulation factor IX showed markedly reduced (albeit not entirely eliminated) CD8+ T cell infiltration upon intramuscular gene transfer in hemophilia B mice when compared to conventional CpG+ vector (comprised of native sequences), resulting in better preservation of transduced muscle fibers. Therefore, this deimmunization strategy is helpful in reducing the potential for CD8+ T cell responses to capsid or transgene product. However, CpG depletion had minimal effects on antibody responses against capsid or transgene product, which appear to be largely independent of CpG motifs.

Published
2021
Full Text
View/download PDF

213. The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma

Author

Zirong Chen, Wei Ni, Jian-Liang Li, Shuibin Lin, Xin Zhou, Yuping Sun, Jennifer W. Li, Marino E. Leon, Maria D. Hurtado, Sergei Zolotukhin, Chen Liu, Jianrong Lu, James D. Griffin, Frederic J. Kaye, and Lizi Wu

Subjects
Oncology, Medicine
Abstract

No effective systemic treatment is available for patients with unresectable, recurrent, or metastatic mucoepidermoid carcinoma (MEC), the most common salivary gland malignancy. MEC is frequently associated with a t(11;19)(q14-21;p12-13) translocation that creates a CRTC1-MAML2 fusion gene. The CRTC1-MAML2 fusion exhibited transforming activity in vitro; however, whether it serves as an oncogenic driver for MEC establishment and maintenance in vivo remains unknown. Here, we show that doxycycline-induced CRTC1-MAML2 knockdown blocked the growth of established MEC xenografts, validating CRTC1-MAML2 as a therapeutic target. We further generated a conditional transgenic mouse model and observed that Cre-induced CRTC1-MAML2 expression caused 100% penetrant formation of salivary gland tumors resembling histological and molecular characteristics of human MEC. Molecular analysis of MEC tumors revealed altered p16-CDK4/6-RB pathway activity as a potential cooperating event in promoting CRTC1-MAML2–induced tumorigenesis. Cotargeting of aberrant p16-CDK4/6-RB signaling and CRTC1-MAML2 fusion–activated AREG/EGFR signaling with the respective CDK4/6 inhibitor Palbociclib and EGFR inhibitor Erlotinib produced enhanced antitumor responses in vitro and in vivo. Collectively, this study provides direct evidence for CRTC1-MAML2 as a key driver for MEC development and maintenance and identifies a potentially novel combination therapy with FDA-approved EGFR and CDK4/6 inhibitors as a potential viable strategy for patients with MEC.

Published
2021
Full Text
View/download PDF

215. Search for New Open Clusters in Huge Catalogues

Author

Zolotukhin, Ivan, Koposov, Sergey, and Glushkova, Elena

Subjects
Astrophysics
Abstract

Current catalogues of open clusters are rather heterogeneous and incomplete lists of clusters than true catalogues. Before there has been no attempts of automatic search for open clusters in huge photometric catalogues using homogeneous all-sky approach. We have developed such a method based on extraction from catalogue and successive analysis of stellar densities using the colour-magnitude diagrams. Our algorithm finds density peaks and then verifies the significance of these peaks exploiting the fact that in real clusters only stars lying on the isochrone must show density peaks, in contrast with stars lying far from the isochrone on the CMD. In addition such procedure allows to determine the physical parameters: age, distance and color excess of open clusters. Preliminary study of 150 sq. degrees in Galaxy anticenter region yielded several dozens of new clusters. The software developed will allow to build first homogeneous all-sky open cluster catalogue (it will include essentially refined data for known clusters as well) based on 2MASS data., Comment: 4 pages, 3 figures, proceedings of ADASS XV, Madrid (Spain), October 2005, Asp. Conf. Ser. 2005 in press, (C.Gabriel, C.Arviset, D.Ponz and E.Solano, eds.)

Published
2006

216. Search for and investigation of new stellar clusters using the data from huge stellar catalogues

Author

Koposov, Sergey, Glushkova, Elena, and Zolotukhin, Ivan

Subjects
Astrophysics
Abstract

We present new automatic methods of search for star clusters using the data available in new huge stellar catalogues. Using 2MASS catalogue we have discovered over ten new open clusters in the region of Galaxy anticenter and determined their physical parameters., Comment: Proceedings of the 79th Annual Scientific Meeting of the Astronomische Gesellschaft, Cologne(Germany), September 2005

Published
2006
Full Text
View/download PDF

221. On Detection of Network-Based Co-residence Verification Attacks in SDN-Driven Clouds

Author

Zolotukhin, Mikhail, Ivannikova, Elena, Hämäläinen, Timo, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Galinina, Olga, editor, Andreev, Sergey, editor, Balandin, Sergey, editor, and Koucheryavy, Yevgeni, editor

Published
2017
Full Text
View/download PDF

222. Probabilistic Transition-Based Approach for Detecting Application-Layer DDoS Attacks in Encrypted Software-Defined Networks

Author

Ivannikova, Elena, Zolotukhin, Mikhail, Hämäläinen, Timo, Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Weikum, Gerhard, Series editor, Yan, Zheng, editor, Molva, Refik, editor, Mazurczyk, Wojciech, editor, and Kantola, Raimo, editor

Published
2017
Full Text
View/download PDF

223. Optical Camera with high temporal resolution to search for transients in the wide field

Author

Karpov, S., Beskin, G., Biryukov, A., Bondar, S., Hurley, K., Ivanov, E., Katkova, E., Pozanenko, A., and Zolotukhin, I.

Subjects
Astrophysics
Abstract

The wide field optical camera with high temporal resolution for the continuous monitoring of the sky in order to catch the initial stages of GRBs is described., Comment: 4 pages, 4 figures. To be published in "Il Nuovo Cimento", Proceedings of the 4th Rome Workshop on Gamma-Ray Bursts in the Afterglow Era, eds. L. Piro, L. Amati, S. Covino, B. Gendre

Published
2005
Full Text
View/download PDF

224. FAVOR (FAst Variability Optical Registration) -- A Two-telescope Complex for Detection and Investigation of Short Optical Transients

Author

Beskin, G., Bad'in, V., Biryukov, A., Bondar, S., Chuntonov, G., Debur, V., Ivanov, E., Karpov, S., Katkova, E., Plokhotnichenko, V., Pozanenko, A., Zolotukhin, I., Hurley, K., Palazzi, E., Masetti, N., Pian, E., Nicastro, L., Bartolini, C., Guarnieri, A., Piccioni, A., Conconi, P., Molinari, E., Zerbi, F. M., Brosch, N., Eichler, D., Shearer, A., Atteia, J. -L., and Boer, M.

Subjects
Astrophysics
Abstract

An astronomical complex intended to detect optical transients (OTs) in a wide field and follow them up with high time resolution investigation is described., Comment: 4 pages, 3 figures. To be published in "Il Nuovo Cimento", Proceedings of the 4th Rome Workshop on Gamma-Ray Bursts in the Afterglow Era, eds. L. Piro, L. Amati, S. Covino, B. Gendre

Published
2005
Full Text
View/download PDF

248. Evaluation of engineered AAV capsids for hepatic factor IX gene transfer in murine and canine models

Author

David M. Markusic, Timothy C. Nichols, Elizabeth P. Merricks, Brett Palaschak, Irene Zolotukhin, Damien Marsic, Sergei Zolotukhin, Arun Srivastava, and Roland W. Herzog

Subjects
AAV, Gene therapy, Hemophilia B, Factor IX, Capsid, Medicine
Abstract

Abstract Background Adeno-associated virus (AAV) gene therapy vectors have shown the best outcomes in human clinical studies for the treatment of genetic diseases such as hemophilia. However, these pivotal investigations have also identified several challenges. For example, high vector doses are often used for hepatic gene transfer, and cytotoxic T lymphocyte responses against viral capsid may occur. Therefore, achieving therapy at reduced vector doses and other strategies to reduce capsid antigen presentation are desirable. Methods We tested several engineered AAV capsids for factor IX (FIX) expression for the treatment of hemophilia B by hepatic gene transfer. These capsids lack potential phosphorylation or ubiquitination sites, or had been generated through molecular evolution. Results AAV2 capsids lacking either a single lysine residue or 3 tyrosine residues directed substantially higher coagulation FIX expression in mice compared to wild-type sequence or other mutations. In hemophilia B dogs, however, expression from the tyrosine-mutant vector was merely comparable to historical data on AAV2. Evolved AAV2-LiC capsid was highly efficient in hemophilia B mice but lacked efficacy in a hemophilia B dog. Conclusions Several alternative strategies for capsid modification improve the in vivo performance of AAV vectors in hepatic gene transfer for correction of hemophilia. However, capsid optimization solely in mouse liver may not predict efficacy in other species and thus is of limited translational utility.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results