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Frank Seeliger
AstraZeneca
18Publications
10H-index
273Citations
Publications 18
Newest
#1Alba Carreras (Sahlgrenska University Hospital)H-Index: 4
#2Luna Simona PaneH-Index: 2
Last.Marcello MarescaH-Index: 6
view all 20 authors...
Background Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target diseas...
1 CitationsSource
#1Stephen Lee (UCLA: University of California, Los Angeles)H-Index: 27
#2Christina Priest (UCLA: University of California, Los Angeles)H-Index: 1
Last.Cynthia Hong (UCLA: University of California, Los Angeles)H-Index: 31
view all 30 authors...
Liver X receptors limit cellular lipid uptake by stimulating the transcription of inducible degrader of the low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase that targets lipoprotein receptors for degradation. The function of IDOL in systemic metabolism is incompletely understood. Here we show that loss of IDOL in mice protects against the development of diet-induced obesity and metabolic dysfunction by altering food intake and thermogenesis. Unexpectedly, analysis of tissue-specif...
Source
#1Pinar Akcakaya (AstraZeneca)H-Index: 3
#2Maggie L. Bobbin (Harvard University)H-Index: 4
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 22 authors...
CRISPR–Cas genome-editing nucleases hold substantial promise for developing human therapeutic applications1–6 but identifying unwanted off-target mutations is important for clinical translation7. A well-validated method that can reliably identify off-targets in vivo has not been described to date, which means it is currently unclear whether and how frequently these mutations occur. Here we describe ‘verification of in vivo off-targets’ (VIVO), a highly sensitive strategy that can robustly identi...
48 CitationsSource
#1Christian JungH-Index: 45
#2Bernhard Wernly (University of Salzburg)H-Index: 7
Last.Qing-Dong Wang (AstraZeneca)H-Index: 24
view all 17 authors...
Abstract Background Oxytocin (Oxt) and its receptor (Oxtr) gene system has been implicated in cardiomyogenesis and cardioprotection; however, effects of chronic activation of Oxtr are not known. We generated and investigated transgenic (TG) mice that overexpress Oxtr specifically in the heart. Methods and Results Cardiac-specific overexpression of Oxtr was obtained by having the α-major histocompatibility complex promoter drive the mouse Oxtr gene (α-Mhc-Oxtr). Left ventricular (LV) function and...
1 CitationsSource
#1Pinar Akcakaya (AstraZeneca)H-Index: 3
#2Maggie L. Bobbin (Harvard University)H-Index: 1
Last.J. Keith Joung (Harvard University)H-Index: 62
view all 22 authors...
CRISPR-Cas genome-editing nucleases hold substantial promise for human therapeutics but identifying unwanted off-target mutations remains an important requirement for clinical translation. For ex vivo therapeutic applications, previously published cell-based genome-wide methods provide potentially useful strategies to identify and quantify these off-target mutation sites. However, a well-validated method that can reliably identify off-targets in vivo has not been described to date, leaving the q...
4 CitationsSource
#1Mikael Bjursell (AstraZeneca)H-Index: 20
#2Michelle J. Porritt (AstraZeneca)H-Index: 4
Last.John Wiseman (AstraZeneca)H-Index: 4
view all 14 authors...
Abstract α1-antitrypsin (AAT) is a circulating serine protease inhibitor secreted from the liver and important in preventing proteolytic neutrophil elastase associated tissue damage, primarily in lungs. In humans, AAT is encoded by the SERPINA1 (hSERPINA1) gene in which a point mutation (commonly referred to as PiZ) causes aggregation of the miss-folded protein in hepatocytes resulting in subsequent liver damage. In an attempt to rescue the pathologic liver phenotype of a mouse model of human AA...
11 CitationsSource
#1Annamaria Brändli-Baiocco (Hoffmann-La Roche)H-Index: 1
#2Emmanuelle Balme (Boehringer Ingelheim)H-Index: 1
Last.Thomas J. Rosol (OU: Ohio University)H-Index: 2
view all 18 authors...
1 CitationsSource
#1Nikolai Klymiuk (LMU: Ludwig Maximilian University of Munich)H-Index: 19
#2Frank Seeliger (AstraZeneca)H-Index: 10
Last.Eckhard Wolf (LMU: Ludwig Maximilian University of Munich)H-Index: 76
view all 6 authors...
Despite enormous advances in translational biomedical research, there remains a growing demand for improved animal models of human disease. This is particularly true for diseases where rodent models do not reflect the human disease phenotype. Compared to rodents, pig anatomy and physiology are more similar to humans in cardiovascular, immune, respiratory, skeletal muscle, and metabolic systems. Importantly, efficient and precise techniques for genetic engineering of pigs are now available, facil...
14 CitationsSource
#1Barbara Albl (LMU: Ludwig Maximilian University of Munich)H-Index: 2
#2Serena Haesner (LMU: Ludwig Maximilian University of Munich)H-Index: 2
Last.Andreas Blutke (LMU: Ludwig Maximilian University of Munich)H-Index: 12
view all 9 authors...
This article provides guidelines for organ and tissue sampling adapted to porcine animal models in translational medical research. Detailed protocols for the determination of sampling locations and numbers as well as recommendations on the orientation, size, and trimming direction of samples from ∼50 different porcine organs and tissues are provided in the Supplementary Material. The proposed sampling protocols include the generation of samples suitable for subsequent qualitative and quantitativ...
15 CitationsSource
#1Uschi Lindert (Boston Children's Hospital)H-Index: 6
#2MaryAnn Weis (UW: University of Washington)H-Index: 36
Last.Cecilia Giunta (Boston Children's Hospital)H-Index: 27
view all 9 authors...
Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI ...
20 CitationsSource
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