LIVIVO - Search results -

Search results

Result 1 - 10 of total 13

Search options

Article: Gene Therapy Approaches to Treat the Neurodegeneration and Visual Failure in Neuronal Ceroid Lipofuscinoses.

Kleine Holthaus, Sophia-Martha / Smith, Alexander J / Mole, Sara E / Ali, Robin R

Advances in experimental medicine and biology

2018 Volume 1074, Page(s) 91–99

Abstract: Neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, inherited lysosomal storage disorders mostly affecting the central nervous system of children. Symptoms include vision loss, seizures, motor deterioration and cognitive decline ultimately ... ...

Abstract	Neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, inherited lysosomal storage disorders mostly affecting the central nervous system of children. Symptoms include vision loss, seizures, motor deterioration and cognitive decline ultimately resulting in premature death. Studies in animal models showed that the diseases are amenable to gene supplementation therapies, and over the last decade, major advances have been made in the (pre)clinical development of these therapies. This mini-review summarises and discusses current gene therapy approaches for NCL targeting the brain and the eye.
MeSH term(s)	Animals ; Brain/enzymology ; Child ; Clinical Trials as Topic ; Dependovirus/genetics ; Disease Models, Animal ; Genetic Therapy/methods ; Genetic Vectors/administration & dosage ; Genetic Vectors/therapeutic use ; Humans ; Infant ; Injections, Intraocular ; Injections, Intraventricular ; Lysosomes/enzymology ; Nerve Degeneration/therapy ; Neuronal Ceroid-Lipofuscinoses/complications ; Neuronal Ceroid-Lipofuscinoses/enzymology ; Neuronal Ceroid-Lipofuscinoses/therapy ; Organ Specificity ; Vision Disorders/etiology ; Vision Disorders/therapy
Language	English
Publishing date	2018-04-12
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-75402-4_12
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Gene Therapy Targeting the Inner Retina Rescues the Retinal Phenotype in a Mouse Model of CLN3 Batten Disease.

Kleine Holthaus, Sophia-Martha / Aristorena, Mikel / Maswood, Ryea / Semenyuk, Olha / Hoke, Justin / Hare, Aura / Smith, Alexander J / Mole, Sara E / Ali, Robin R

Human gene therapy

2020 Volume 31, Issue 13-14, Page(s) 709–718

Abstract: The neuronal ceroid lipofuscinoses (NCLs), often referred to as Batten disease, are inherited lysosomal storage disorders that represent the most common neurodegeneration during childhood. Symptoms include seizures, vision loss, motor and cognitive ... ...

Abstract	The neuronal ceroid lipofuscinoses (NCLs), often referred to as Batten disease, are inherited lysosomal storage disorders that represent the most common neurodegeneration during childhood. Symptoms include seizures, vision loss, motor and cognitive decline, and premature death. The development of brain-directed treatments for NCLs has made noteworthy progress in recent years. Clinical trials are currently ongoing or planned for different forms of the disease. Despite these promising advances, it is unlikely that therapeutic interventions targeting the brain will prevent loss of vision in patients as retinal cells remain untreated and will continue to degenerate. Here, we demonstrate that
MeSH term(s)	Animals ; Dependovirus/genetics ; Disease Models, Animal ; Genetic Therapy/methods ; Membrane Glycoproteins/genetics ; Mice ; Mice, Inbred C57BL ; Molecular Chaperones/genetics ; Neuronal Ceroid-Lipofuscinoses/complications ; Phenotype ; Photoreceptor Cells/metabolism ; Retinal Diseases/etiology ; Retinal Diseases/metabolism ; Retinal Diseases/pathology ; Retinal Diseases/therapy
Chemical Substances	CLN3 protein, mouse ; Membrane Glycoproteins ; Molecular Chaperones
Language	English
Publishing date	2020-06-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2020.038
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2988: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Experimental gene therapies for the NCLs.

Liu, Wenfei / Kleine-Holthaus, Sophia-Martha / Herranz-Martin, Saul / Aristorena, Mikel / Mole, Sara E / Smith, Alexander J / Ali, Robin R / Rahim, Ahad A

Biochimica et biophysica acta. Molecular basis of disease

2020 Volume 1866, Issue 9, Page(s) 165772

Abstract: The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of rare monogenic neurodegenerative diseases predominantly affecting children. All NCLs are lethal and incurable and only one has an approved treatment available. To ... ...

Abstract	The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of rare monogenic neurodegenerative diseases predominantly affecting children. All NCLs are lethal and incurable and only one has an approved treatment available. To date, 13 NCL subtypes (CLN1-8, CLN10-14) have been identified, based on the particular disease-causing defective gene. The exact functions of NCL proteins and the pathological mechanisms underlying the diseases are still unclear. However, gene therapy has emerged as an attractive therapeutic strategy for this group of conditions. Here we provide a short review discussing updates on the current gene therapy studies for the NCLs.
MeSH term(s)	Animals ; Genetic Therapy ; Humans ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/therapy
Language	English
Publishing date	2020-03-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2020.165772
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.247: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Clinical challenges and future therapeutic approaches for neuronal ceroid lipofuscinosis.

Mole, Sara E / Anderson, Glenn / Band, Heather A / Berkovic, Samuel F / Cooper, Jonathan D / Kleine Holthaus, Sophia-Martha / McKay, Tristan R / Medina, Diego L / Rahim, Ahad A / Schulz, Angela / Smith, Alexander J

The Lancet. Neurology

2018 Volume 18, Issue 1, Page(s) 107–116

Abstract: Treatment of the neuronal ceroid lipofuscinoses, also known as Batten disease, is at the start of a new era because of diagnostic and therapeutic advances relevant to this group of inherited neurodegenerative and life-limiting disorders that affect ... ...

Abstract	Treatment of the neuronal ceroid lipofuscinoses, also known as Batten disease, is at the start of a new era because of diagnostic and therapeutic advances relevant to this group of inherited neurodegenerative and life-limiting disorders that affect children. Diagnosis has improved with the use of comprehensive DNA-based tests that simultaneously screen for many genes. The identification of disease-causing mutations in 13 genes provides a basis for understanding the molecular mechanisms underlying neuronal ceroid lipofuscinoses, and for the development of targeted therapies. These targeted therapies include enzyme replacement therapies, gene therapies targeting the brain and the eye, cell therapies, and pharmacological drugs that could modulate defective molecular pathways. Such therapeutic developments have the potential to enable earlier diagnosis and better targeted therapeutic management. The first approved treatment is an intracerebroventricularly administered enzyme for neuronal ceroid lipofuscinosis type 2 disease that delays symptom progression. Efforts are underway to make similar progress for other forms of the disorder.
MeSH term(s)	Disease Progression ; Enzyme Replacement Therapy ; Genetic Therapy/methods ; Humans ; Mutation ; Neuronal Ceroid-Lipofuscinoses/drug therapy ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/therapy
Language	English
Publishing date	2018-11-21
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2081241-3
ISSN	1474-4465 ; 1474-4422
ISSN (online)	1474-4465
ISSN	1474-4422
DOI	10.1016/S1474-4422(18)30368-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5955: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Neonatal brain-directed gene therapy rescues a mouse model of neurodegenerative CLN6 Batten disease.

Kleine Holthaus, Sophia-Martha / Herranz-Martin, Saul / Massaro, Giulia / Aristorena, Mikel / Hoke, Justin / Hughes, Michael P / Maswood, Ryea / Semenyuk, Olha / Basche, Mark / Shah, Amna Z / Klaska, Izabela P / Smith, Alexander J / Mole, Sara E / Rahim, Ahad A / Ali, Robin R

Human molecular genetics

2019 Volume 28, Issue 23, Page(s) 3867–3879

Abstract: The neuronal ceroid lipofuscinoses (NCLs), more commonly referred to as Batten disease, are a group of inherited lysosomal storage disorders that present with neurodegeneration, loss of vision and premature death. There are at least 13 genetically ... ...

Abstract	The neuronal ceroid lipofuscinoses (NCLs), more commonly referred to as Batten disease, are a group of inherited lysosomal storage disorders that present with neurodegeneration, loss of vision and premature death. There are at least 13 genetically distinct forms of NCL. Enzyme replacement therapies and pre-clinical studies on gene supplementation have shown promising results for NCLs caused by lysosomal enzyme deficiencies. The development of gene therapies targeting the brain for NCLs caused by defects in transmembrane proteins has been more challenging and only limited therapeutic effects in animal models have been achieved so far. Here, we describe the development of an adeno-associated virus (AAV)-mediated gene therapy to treat the neurodegeneration in a mouse model of CLN6 disease, a form of NCL with a deficiency in the membrane-bound protein CLN6. We show that neonatal bilateral intracerebroventricular injections with AAV9 carrying CLN6 increase lifespan by more than 90%, maintain motor skills and motor coordination and reduce neuropathological hallmarks of Cln6-deficient mice up to 23 months post vector administration. These data demonstrate that brain-directed gene therapy is a valid strategy to treat the neurodegeneration of CLN6 disease and may be applied to other forms of NCL caused by transmembrane protein deficiencies in the future.
MeSH term(s)	Animals ; Animals, Newborn ; Brain/growth & development ; Dependovirus/genetics ; Disease Models, Animal ; Genetic Therapy ; Genetic Vectors/administration & dosage ; Humans ; Injections, Intraventricular ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/metabolism ; Neuronal Ceroid-Lipofuscinoses/therapy ; Treatment Outcome
Chemical Substances	CLN6 protein, human ; Membrane Proteins
Language	English
Publishing date	2019-12-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddz210
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3469: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Use of model organisms for the study of neuronal ceroid lipofuscinosis.

Bond, Michael / Holthaus, Sophia-Martha Kleine / Tammen, Imke / Tear, Guy / Russell, Claire

Biochimica et biophysica acta

2013 Volume 1832, Issue 11, Page(s) 1842–1865

Abstract: Neuronal ceroid lipofuscinoses are a group of fatal progressive neurodegenerative diseases predominantly affecting children. Identification of mutations that cause neuronal ceroid lipofuscinosis, and subsequent functional and pathological studies of the ... ...

Abstract	Neuronal ceroid lipofuscinoses are a group of fatal progressive neurodegenerative diseases predominantly affecting children. Identification of mutations that cause neuronal ceroid lipofuscinosis, and subsequent functional and pathological studies of the affected genes, underpins efforts to investigate disease mechanisms and identify and test potential therapeutic strategies. These functional studies and pre-clinical trials necessitate the use of model organisms in addition to cell and tissue culture models as they enable the study of protein function within a complex organ such as the brain and the testing of therapies on a whole organism. To this end, a large number of disease models and genetic tools have been identified or created in a variety of model organisms. In this review, we will discuss the ethical issues associated with experiments using model organisms, the factors underlying the choice of model organism, the disease models and genetic tools available, and the contributions of those disease models and tools to neuronal ceroid lipofuscinosis research. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease.
MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Membrane Proteins/genetics ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/pathology
Chemical Substances	Membrane Proteins
Language	English
Publishing date	2013-11
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2013.01.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uc I Zs.247: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Prevention of Photoreceptor Cell Loss in a Cln6

Kleine Holthaus, Sophia-Martha / Ribeiro, Joana / Abelleira-Hervas, Laura / Pearson, Rachael A / Duran, Yanai / Georgiadis, Anastasios / Sampson, Robert D / Rizzi, Matteo / Hoke, Justin / Maswood, Ryea / Azam, Selina / Luhmann, Ulrich F O / Smith, Alexander J / Mole, Sara E / Ali, Robin R

Molecular therapy : the journal of the American Society of Gene Therapy

2018 Volume 26, Issue 5, Page(s) 1343–1353

Abstract: The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is ... ...

Abstract	The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. We found that, although Cln6
MeSH term(s)	Animals ; Dependovirus/genetics ; Disease Models, Animal ; Gene Expression ; Gene Transfer Techniques ; Genetic Therapy ; Genetic Vectors/genetics ; Humans ; Immunohistochemistry ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Mice ; Mice, Transgenic ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/metabolism ; Neuronal Ceroid-Lipofuscinoses/pathology ; Neuronal Ceroid-Lipofuscinoses/therapy ; Photoreceptor Cells/metabolism ; Photoreceptor Cells/pathology ; Retinal Bipolar Cells/metabolism
Chemical Substances	Cln6 protein, mouse ; Membrane Proteins
Language	English
Publishing date	2018-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2018.02.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model.

Chu, Colin J / Gardner, Peter J / Copland, David A / Liyanage, Sidath E / Gonzalez-Cordero, Anai / Kleine Holthaus, Sophia-Martha / Luhmann, Ulrich F O / Smith, Alexander J / Ali, Robin R / Dick, Andrew D

Disease models & mechanisms

2016 Volume 9, Issue 4, Page(s) 473–481

Abstract: Endotoxin-induced uveitis (EIU) in rodents is a model of acute Toll-like receptor 4 (TLR4)-mediated organ inflammation, and has been used to model human anterior uveitis, examine leukocyte trafficking and test novel anti-inflammatory therapeutics. Wider ... ...

Abstract	Endotoxin-induced uveitis (EIU) in rodents is a model of acute Toll-like receptor 4 (TLR4)-mediated organ inflammation, and has been used to model human anterior uveitis, examine leukocyte trafficking and test novel anti-inflammatory therapeutics. Wider adoption has been limited by the requirement for manual, non-specific, cell-count scoring of histological sections from each eye as a measure of disease severity. Here, we describe a comprehensive and efficient technique that uses ocular dissection and multimodal tissue analysis. This allows matched disease scoring by multicolour flow cytometric analysis of the inflammatory infiltrate, protein analysis on ocular supernatants and qPCR on remnant tissues of the same eye. Dynamic changes in cell populations could be identified and mapped to chemokine and cytokine changes over the course of the model. To validate the technique, dose-responsive suppression of leukocyte infiltration by recombinant interleukin-10 was demonstrated, as well as selective suppression of the monocyte (CD11b+Ly6C+) infiltrate, in mice deficient for eitherCcl2orCcr2 Optical coherence tomography (OCT) was used for the first time in this model to allowin vivoimaging of infiltrating vitreous cells, and correlated with CD11b+Ly6G+ counts to provide another unique measure of cell populations in the ocular tissue. Multimodal tissue analysis of EIU is proposed as a new standard to improve and broaden the application of this model.
MeSH term(s)	Animals ; Cell Count ; Chemokine CCL2/metabolism ; Cytokines/metabolism ; Disease Models, Animal ; Endotoxins ; Eye/pathology ; Female ; Flow Cytometry ; Inflammation/pathology ; Mice, Inbred C57BL ; Neutrophil Infiltration ; Neutrophils/pathology ; Receptors, CCR2/deficiency ; Receptors, CCR2/metabolism ; Severity of Illness Index ; Tomography, Optical Coherence ; Uveitis/chemically induced ; Uveitis/pathology
Chemical Substances	Ccr2 protein, mouse ; Chemokine CCL2 ; Cytokines ; Endotoxins ; Receptors, CCR2
Language	English
Publishing date	2016-01-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.022475
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Multimodal analysis of ocular inflammation using the endotoxin-induced uveitis mouse model

Colin J. Chu / Peter J. Gardner / David A. Copland / Sidath E. Liyanage / Anai Gonzalez-Cordero / Sophia-Martha kleine Holthaus / Ulrich F. O. Luhmann / Alexander J. Smith / Robin R. Ali / Andrew D. Dick

Disease Models & Mechanisms, Vol 9, Iss 4, Pp 473-

2016 Volume 481

Abstract	Endotoxin-induced uveitis (EIU) in rodents is a model of acute Toll-like receptor 4 (TLR4)-mediated organ inflammation, and has been used to model human anterior uveitis, examine leukocyte trafficking and test novel anti-inflammatory therapeutics. Wider adoption has been limited by the requirement for manual, non-specific, cell-count scoring of histological sections from each eye as a measure of disease severity. Here, we describe a comprehensive and efficient technique that uses ocular dissection and multimodal tissue analysis. This allows matched disease scoring by multicolour flow cytometric analysis of the inflammatory infiltrate, protein analysis on ocular supernatants and qPCR on remnant tissues of the same eye. Dynamic changes in cell populations could be identified and mapped to chemokine and cytokine changes over the course of the model. To validate the technique, dose-responsive suppression of leukocyte infiltration by recombinant interleukin-10 was demonstrated, as well as selective suppression of the monocyte (CD11b+Ly6C+) infiltrate, in mice deficient for either Ccl2 or Ccr2. Optical coherence tomography (OCT) was used for the first time in this model to allow in vivo imaging of infiltrating vitreous cells, and correlated with CD11b+Ly6G+ counts to provide another unique measure of cell populations in the ocular tissue. Multimodal tissue analysis of EIU is proposed as a new standard to improve and broaden the application of this model.
Keywords	EIU ; Flow cytometry ; OCT ; Medicine ; R ; Pathology ; RB1-214
Subject code	610
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Assessment of AAV Vector Tropisms for Mouse and Human Pluripotent Stem Cell-Derived RPE and Photoreceptor Cells.

Gonzalez-Cordero, Anai / Goh, Debbie / Kruczek, Kamil / Naeem, Arifa / Fernando, Milan / Kleine Holthaus, Sophia-Martha / Takaaki, Matsuki / Blackford, Samuel J I / Kloc, Magdalena / Agundez, Leticia / Sampson, Robert D / Borooah, Shyamanga / Ovando-Roche, Patrick / Mehat, Manjit S / West, Emma L / Smith, Alexander J / Pearson, Rachael A / Ali, Robin R

Human gene therapy

2018 Volume 29, Issue 10, Page(s) 1124–1139

Abstract: Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in ... ...

Abstract	Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem cell-derived retina now offers the possibility to assess efficacy in human organoids in vitro. Here we test six adeno-associated virus (AAV) serotypes [AAV2/2, AAV2/9, AAV2/8, AAV2/8T(Y733F), AAV2/5, and ShH10] to determine their efficiency in transducing mouse and human pluripotent stem cell-derived retinal pigment epithelium (RPE) and photoreceptor cells in vitro. All the serotypes tested were capable of transducing RPE and photoreceptor cells in vitro. AAV ShH10 and AAV2/5 are the most efficient vectors at transducing both mouse and human RPE, while AAV2/8 and ShH10 achieved similarly robust transduction of human embryonic stem cell-derived cone photoreceptors. Furthermore, we show that human embryonic stem cell-derived photoreceptors can be used to establish promoter specificity in human cells in vitro. The results of this study will aid capsid selection and vector design for preclinical evaluation of gene therapy approaches, such as gene editing, that require the use of human cells and tissues.
MeSH term(s)	Animals ; Cell Differentiation ; Cells, Cultured ; Dependovirus/classification ; Dependovirus/physiology ; Fluorescent Antibody Technique ; Gene Expression ; Gene Transfer Techniques ; Genes, Reporter ; Genetic Vectors/genetics ; Humans ; Mice ; Organ Specificity/genetics ; Photoreceptor Cells/cytology ; Photoreceptor Cells/metabolism ; Pluripotent Stem Cells/cytology ; Promoter Regions, Genetic ; Retinal Pigment Epithelium/cytology ; Transduction, Genetic ; Transgenes ; Viral Tropism
Language	English
Publishing date	2018-05-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2018.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2988: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito