LIVIVO - Search results -

Search results

Result 1 - 10 of total 140

Search options

Article ; Online: Givosiran - Running RNA Interference to Fight Porphyria Attacks.

Gonzalez-Aseguinolaza, Gloria

2020 Volume 382, Issue 24, Page(s) 2366–2367

MeSH term(s)	Acetylgalactosamine/analogs & derivatives ; Humans ; Porphyria, Acute Intermittent ; Porphyrias ; Pyrrolidines ; RNA Interference ; RNAi Therapeutics ; Running
Chemical Substances	Pyrrolidines ; Acetylgalactosamine (KM15WK8O5T) ; givosiran (ROV204583W)
Language	English
Publishing date	2020-06-10
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMe2010986
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.34: 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

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.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Gene therapy for liver diseases - progress and challenges.

Zabaleta, Nerea / Unzu, Carmen / Weber, Nicholas D / Gonzalez-Aseguinolaza, Gloria

Nature reviews. Gastroenterology & hepatology

2023 Volume 20, Issue 5, Page(s) 288–305

Abstract: Gene therapy is poised to revolutionize modern medicine, with seemingly unlimited potential for treating and curing genetic disorders. For otherwise incurable indications, including most inherited metabolic liver disorders, gene therapy provides a ... ...

Abstract	Gene therapy is poised to revolutionize modern medicine, with seemingly unlimited potential for treating and curing genetic disorders. For otherwise incurable indications, including most inherited metabolic liver disorders, gene therapy provides a realistic therapeutic option. In this Review, we discuss gene supplementation and gene editing involving the use of recombinant adeno-associated virus (rAAV) vectors for the treatment of inherited liver diseases, including updates on several ongoing clinical trials that are producing promising results. Clinical testing has been essential in highlighting many key translational challenges associated with this transformative therapy. In particular, the interaction of a patient's immune system with the vector raises issues of safety and the duration of treatment efficacy. Furthermore, several serious adverse events after the administration of high doses of rAAVs suggest greater involvement of innate immune responses and pre-existing hepatic conditions than initially anticipated. Finally, permanent modification of the host genome associated with rAAV genome integration and gene editing raises concerns about the risk of oncogenicity that require careful evaluation. We summarize the main progress, challenges and pathways forward for gene therapy for liver diseases.
MeSH term(s)	Humans ; Genetic Vectors ; Genetic Therapy/methods ; Liver Diseases/genetics ; Liver Diseases/therapy ; Immunity, Innate
Language	English
Publishing date	2023-01-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-022-00729-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6020: 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)
Zs.MG 97: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Deciphering the Role of Post-Translational Modifications and Cellular Location of Hepatitis Delta Virus (HDV) Antigens in HDV-Mediated Liver Damage in Mice.

Maestro, Sheila / Gomez-Echarte, Nahia / Camps, Gracian / Usai, Carla / Olagüe, Cristina / Vales, Africa / Aldabe, Rafael / Gonzalez-Aseguinolaza, Gloria

Viruses

2024 Volume 16, Issue 3

Abstract: Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adeno-associated virus (AAV-HDV) as gene delivery vehicles offers ... ...

Abstract	Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adeno-associated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investigate the molecular aspects of HDV and associated liver damage. For the purpose of this study, we generated HDV genomes modified by site-directed mutagenesis aimed to (i) prevent some post-translational modifications of HDV antigens (HDAgs) such as large-HDAg (L-HDAg) isoprenylation or short-HDAg (S-HDAg) phosphorylation; (ii) alter the localization of HDAgs within the subcellular compartments; and (iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser177 phosphorylation and ribozymal activity are essential for HDV replication and HDAg expression. Mutations of the isoprenylation domain prevented the formation of infectious particles and increased cellular toxicity and liver damage. Furthermore, altering HDAg intracellular localization notably decreased viral replication, though liver damage remained unchanged versus normal HDAg distribution. In addition, a mutation in the nuclear export signal impaired the formation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations.
MeSH term(s)	Animals ; Mice ; Hepatitis delta Antigens/genetics ; Hepatitis delta Antigens/metabolism ; Hepatitis Delta Virus ; RNA, Viral/metabolism ; Mice, Inbred C57BL ; Virus Replication/genetics ; Protein Processing, Post-Translational ; Liver/metabolism
Chemical Substances	Hepatitis delta Antigens ; RNA, Viral
Language	English
Publishing date	2024-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16030379
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Acute Intermittent Porphyria: Novel Etiologic and Pathogenic Therapies Based on RNA Transfer to the Liver.

Prieto, Jesus / Gonzalez-Aseguinolaza, Gloria

Hepatology (Baltimore, Md.)

2019 Volume 70, Issue 3, Page(s) 1061–1063

MeSH term(s)	Humans ; Porphyria, Acute Intermittent ; RNA ; RNA, Messenger
Chemical Substances	RNA, Messenger ; RNA (63231-63-0)
Language	English
Publishing date	2019-05-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.30678
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 1660: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Spanish Society of Gene and Cell Therapy.

González Aseguinolaza, Gloria / Izeta, Ander / Martin Molina, Francisco

Human gene therapy

2021 Volume 32, Issue 23-24, Page(s) 1425–1426

MeSH term(s)	Cell- and Tissue-Based Therapy ; Spain
Language	English
Publishing date	2021-12-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	1028152-6
ISSN	1557-7422 ; 1043-0342
ISSN (online)	1557-7422
ISSN	1043-0342
DOI	10.1089/hum.2021.29190.gga
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: mRNA and gene editing: Late breaking therapies in liver diseases.

Zabaleta, Nerea / Torella, Laura / Weber, Nicholas D / Gonzalez-Aseguinolaza, Gloria

Hepatology (Baltimore, Md.)

2022 Volume 76, Issue 3, Page(s) 869–887

Abstract: The efficient delivery of RNA molecules to restore the expression of a missing or inadequately functioning protein in a target cell and the intentional specific modification of the host genome using engineered nucleases represent therapeutic concepts ... ...

Abstract	The efficient delivery of RNA molecules to restore the expression of a missing or inadequately functioning protein in a target cell and the intentional specific modification of the host genome using engineered nucleases represent therapeutic concepts that are revolutionizing modern medicine. The initiation of several clinical trials using these approaches to treat metabolic liver disorders as well as the recently reported remarkable results obtained by patients with transthyretin amyloidosis highlight the advances in this field and show the potential of these therapies to treat these diseases safely and efficaciously. These advances have been possible due, firstly, to significant improvements made in RNA chemistry that increase its stability and prevent activation of the innate immune response and, secondly, to the development of very efficient liver-targeted RNA delivery systems. In parallel, the breakout of CRISPR/CRISPR-associated 9-based technology in the gene editing field has marked a turning point in in vivo modification of the cellular genome with therapeutic purposes, which can be based on gene supplementation, correction, or silencing. In the coming years we are likely to witness the therapeutic potential of these two strategies both separately and in combination. In this review we summarize the preclinical data obtained in animal models treated with mRNA as a therapeutic agent and discuss the different gene editing strategies applied to the treatment of liver diseases, highlighting both their therapeutic efficacy as well as safety concerns.
MeSH term(s)	Animals ; CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Editing/methods ; Liver Diseases/genetics ; Liver Diseases/therapy ; RNA, Messenger/genetics
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.32441
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 1660: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Comment on "Synthetic human ABCB4 mRNA therapy rescues severe liver disease phenotype in a BALB/c.Abcb4

Weber, Nicholas D / Martínez-García, Javier / González-Aseguinolaza, Gloria

Journal of hepatology

2021 Volume 76, Issue 3, Page(s) 749–751

MeSH term(s)	Animals ; Cholestasis, Intrahepatic/genetics ; Humans ; Mice ; Phenotype ; RNA, Messenger/genetics
Chemical Substances	RNA, Messenger
Language	English
Publishing date	2021-10-06
Publishing country	Netherlands
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2021.09.033
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 2027: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Gene Therapy for Acquired and Genetic Cholestasis.

Martínez-García, Javier / Molina, Angie / González-Aseguinolaza, Gloria / Weber, Nicholas D / Smerdou, Cristian

Biomedicines

2022 Volume 10, Issue 6

Abstract: Cholestatic diseases can be caused by the dysfunction of transporters involved in hepatobiliary circulation. Although pharmacological treatments constitute the current standard of care for these diseases, none are curative, with liver transplantation ... ...

Abstract	Cholestatic diseases can be caused by the dysfunction of transporters involved in hepatobiliary circulation. Although pharmacological treatments constitute the current standard of care for these diseases, none are curative, with liver transplantation being the only long-term solution for severe cholestasis, albeit with many disadvantages. Liver-directed gene therapy has shown promising results in clinical trials for genetic diseases, and it could constitute a potential new therapeutic approach for cholestatic diseases. Many preclinical gene therapy studies have shown positive results in animal models of both acquired and genetic cholestasis. The delivery of genes that reduce apoptosis or fibrosis or improve bile flow has shown therapeutic effects in rodents in which cholestasis was induced by drugs or bile duct ligation. Most studies targeting inherited cholestasis, such as progressive familial intrahepatic cholestasis (PFIC), have focused on supplementing a correct version of a mutated gene to the liver using viral or non-viral vectors in order to achieve expression of the therapeutic protein. These strategies have generated promising results in treating PFIC3 in mouse models of the disease. However, important challenges remain in translating this therapy to the clinic, as well as in developing gene therapy strategies for other types of acquired and genetic cholestasis.
Language	English
Publishing date	2022-05-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10061238
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Understanding and Tackling Immune Responses to Adeno-Associated Viral Vectors.

Costa-Verdera, Helena / Unzu, Carmen / Valeri, Erika / Adriouch, Sahil / González Aseguinolaza, Gloria / Mingozzi, Federico / Kajaste-Rudnitski, Anna

Human gene therapy

2023 Volume 34, Issue 17-18, Page(s) 836–852

Abstract: As the clinical experience in adeno-associated viral (AAV) vector-based gene therapies is expanding, the necessity to better understand and control the host immune responses is also increasing. Immunogenicity of AAV vectors in humans has been linked to ... ...

Abstract	As the clinical experience in adeno-associated viral (AAV) vector-based gene therapies is expanding, the necessity to better understand and control the host immune responses is also increasing. Immunogenicity of AAV vectors in humans has been linked to several limitations of the platform, including lack of efficacy due to antibody-mediated neutralization, tissue inflammation, loss of transgene expression, and in some cases, complement activation and acute toxicities. Nevertheless, significant knowledge gaps remain in our understanding of the mechanisms of immune responses to AAV gene therapies, further hampered by the failure of preclinical animal models to recapitulate clinical findings. In this review, we focus on the current knowledge regarding immune responses, spanning from innate immunity to humoral and adaptive responses, triggered by AAV vectors and how they can be mitigated for safer, durable, and more effective gene therapies.
MeSH term(s)	Animals ; Humans ; Complement Activation ; Immunity, Innate ; Genetic Therapy ; Inflammation ; Models, Animal
Language	English
Publishing date	2023-09-06
Publishing country	United States
Document type	Journal Article ; Review ; 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.2023.119
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: Protective role of RIPK1 scaffolding against HDV-induced hepatocyte cell death and the significance of cytokines in mice.

Camps, Gracián / Maestro, Sheila / Torella, Laura / Herrero, Diego / Usai, Carla / Bilbao-Arribas, Martin / Aldaz, Ana / Olagüe, Cristina / Vales, Africa / Suárez-Amarán, Lester / Aldabe, Rafael / Gonzalez-Aseguinolaza, Gloria

PLoS pathogens

2024 Volume 20, Issue 5, Page(s) e1011749

Abstract: Hepatitis delta virus (HDV) infection represents the most severe form of human viral hepatitis; however, the mechanisms underlying its pathology remain incompletely understood. We recently developed an HDV mouse model by injecting adeno-associated viral ... ...

Abstract	Hepatitis delta virus (HDV) infection represents the most severe form of human viral hepatitis; however, the mechanisms underlying its pathology remain incompletely understood. We recently developed an HDV mouse model by injecting adeno-associated viral vectors (AAV) containing replication-competent HBV and HDV genomes. This model replicates many features of human infection, including liver injury. Notably, the extent of liver damage can be diminished with anti-TNF-α treatment. Here, we found that TNF-α is mainly produced by macrophages. Downstream of the TNF-α receptor (TNFR), the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) serves as a cell fate regulator, playing roles in both cell survival and death pathways. In this study, we explored the function of RIPK1 and other host factors in HDV-induced cell death. We determined that the scaffolding function of RIPK1, and not its kinase activity, offers partial protection against HDV-induced apoptosis. A reduction in RIPK1 expression in hepatocytes through CRISPR-Cas9-mediated gene editing significantly intensifies HDV-induced damage. Contrary to our expectations, the protective effect of RIPK1 was not linked to TNF-α or macrophage activation, as their absence did not alter the extent of damage. Intriguingly, in the absence of RIPK1, macrophages confer a protective role. However, in animals unresponsive to type-I IFNs, RIPK1 downregulation did not exacerbate the damage, suggesting RIPK1's role in shielding hepatocytes from type-I IFN-induced cell death. Interestingly, while the damage extent is similar between IFNAR KO and WT mice in terms of transaminase elevation, their cell death mechanisms differ. In conclusion, our findings reveal that HDV-induced type-I IFN production is central to inducing hepatocyte death, and RIPK1's scaffolding function offers protective benefits. Thus, type-I IFN together with TNF-α, contribute to HDV-induced liver damage. These insights may guide the development of novel therapeutic strategies to mitigate HDV-induced liver damage and halt disease progression.
Language	English
Publishing date	2024-05-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011749
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

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

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

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

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito