Production of Adeno-Associated Virus Vectors in Cell Stacks for Preclinical Studies in Large Animal Models

10.3791/62727 ◽  
2021 ◽  
Author(s):  
Amira D. Rghei ◽  
Brenna A. Y. Stevens ◽  
Sylvia P. Thomas ◽  
Jacob G. E. Yates ◽  
Benjamin M. McLeod ◽  
...  
Keyword(s):  
Animal Models ◽  
Large Animal ◽  
Preclinical Studies ◽  
Adeno Associated Virus ◽  
Virus Vectors ◽  
Large Animal Models

scholarly journals Preclinical Models for Skeletal Research: How Commonly Used Species Mimic (or Don’t) Aspects of Human Bone

2017 ◽  
Vol 45 (7) ◽  
pp. 851-854 ◽  
Author(s):  
Matthew R. Allen
Keyword(s):  
Animal Models ◽  
Bone Growth ◽  
Human Bone ◽  
Large Animal ◽  
Preclinical Studies ◽  
Preclinical Models ◽  
Biological Regulation ◽  
Large Animal Models ◽  
Age Related ◽  
Age Related Changes

Preclinical studies play an indispensable role in exploring the biological regulation of the musculoskeletal system. They are required in all drug development pipelines where both small and large animal models are needed to understand efficacy and side effects. This brief review highlights 4 aspects of human bone, longitudinal bone growth, intracortical remodeling, collagen/mineral interface, and age-related changes, and discusses how various animal models recapitulate (or don’t) these aspects of human skeletal physiology.

scholarly journals Safety and Tolerability of the Adeno-Associated Virus Vector, AAV6.2FF, Expressing a Monoclonal Antibody in Murine and Ovine Animal Models

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1186
Author(s):  
Amira D. Rghei ◽  
Laura P. van Lieshout ◽  
Benjamin M. McLeod ◽  
Yanlong Pei ◽  
Jordyn A. Lopes ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Animal Model ◽  
Animal Models ◽  
Human Monoclonal Antibody ◽  
Scale Up ◽  
Large Animal Model ◽  
Large Animal ◽  
Aav Vector ◽  
Adeno Associated Virus ◽  
Large Animal Models

Adeno-associated virus (AAV) vector mediated expression of therapeutic monoclonal antibodies is an alternative strategy to traditional vaccination to generate immunity in immunosuppressed or immunosenescent individuals. In this study, we vectorized a human monoclonal antibody (31C2) directed against the spike protein of SARS-CoV-2 and determined the safety profile of this AAV vector in mice and sheep as a large animal model. In both studies, plasma biochemical parameters and hematology were comparable to untreated controls. Except for mild myositis at the site of injection, none of the major organs revealed any signs of toxicity. AAV-mediated human IgG expression increased steadily throughout the 28-day study in sheep, resulting in peak concentrations of 21.4–46.7 µg/ mL, demonstrating practical scale up from rodent to large animal models. This alternative approach to immunity is worth further exploration after this demonstration of safety, tolerability, and scalability in a large animal model.

scholarly journals Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence

2021 ◽  
Vol 22 (11) ◽  
pp. 6092
Author(s):  
Bastian Amend ◽  
Niklas Harland ◽  
Jasmin Knoll ◽  
Arnulf Stenzl ◽  
Wilhelm K. Aicher
Keyword(s):  
Urinary Incontinence ◽  
Stress Urinary Incontinence ◽  
Animal Models ◽  
Clinical Situation ◽  
Surgical Instruments ◽  
Health Concern ◽  
Large Animal ◽  
Knock Out ◽  
Cell Therapies ◽  
Large Animal Models

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.

Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes

2017 ◽  
Vol 28 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Lan Huang ◽  
Fengyan Zhao ◽  
Yi Qu ◽  
Li Zhang ◽  
Yan Wang ◽  
...  
Keyword(s):  
Animal Models ◽  
Small Animal ◽  
Underlying Disease ◽  
Therapeutic Interventions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Large Animal ◽  
Large Animal Models ◽  
Neurological Research ◽  
Serious Disease ◽  
Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models.

Echocardiography Evaluation of a Novel Stable Ovine Heart Failure Model Suitable for Cardiovascular Device Testing

2011 ◽  
Author(s):  
Peter W. Walsh ◽  
Craig S. McLachlan ◽  
Leigh Ladd ◽  
Arie Blitz ◽  
R. Mark Gillies ◽  
...  
Keyword(s):  
Heart Failure ◽  
Animal Models ◽  
Large Animal ◽  
Failure Model ◽  
Large Animal Models ◽  
Surgical Model ◽  
Coronary Ligation ◽  
Rapid Ventricular Pacing ◽  
Heart Failure Model ◽  
Underlying Pathology

Numerous large animal models of chronic cardiac ischemia have been developed to explore either pathological mechanisms and or device interventions in developed heart failure models. Traditionally chronic heart failure in large animal models such as sheep or pigs has been induced by either coronary ligation with or without reperfusion. Coronary ligation is often attempted in the open chest surgical model or more recently in the closed chest animal via angiography [1]. Both techniques can be challenging and also induce high mortality with the risk of myocardial stunning and resultant shock and or lethal arrhythmias. There is also difficulty in developing stable heart failure across cases where infarct sizes can be variable. One strategy to over come this variability has been via rapid ventricular pacing, however inducing heart failure does not induce sustained heart failure in many cases if the pacing is switched off, and additionally pacing does not induce some of the underlying pathology seen in the development of heart failure [1].

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