scholarly journals Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

2020 ◽  
Vol 10 (20) ◽  
pp. 7369
Author(s):  
Jun Song ◽  
Brooke Pallas ◽  
Dongshan Yang ◽  
Jifeng Zhang ◽  
Yash Agarwal ◽  
...  
Keyword(s):  
Gene Editing ◽  
Interleukin 2 ◽  
Current Status ◽  
Loss Of Function ◽  
Future Perspectives ◽  
Transcription Activator ◽  
Immune Genes ◽  
Forkhead Box ◽  
Recombination Activating Gene ◽  
Model Family

Production of immunodeficient (ID) models in non-murine animal species had been extremely challenging until the advent of gene-editing tools: first zinc finger nuclease (ZFN), then transcription activator-like effector nuclease (TALEN), and most recently clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR)/Cas9. We and others used those gene-editing tools to develop ID rabbits carrying a loss of function mutation in essential immune genes, such as forkhead box protein N1 (FOXN1), recombination activating gene 1/2 (RAG1/2), and interleukin 2 receptor subunit gamma (IL2RG). Like their mouse counterparts, ID rabbits have profound defects in their immune system and are prone to bacterial and pneumocystis infections without prophylactic antibiotics. In addition to their use as preclinical models for primary immunodeficient diseases, ID rabbits are expected to contribute significantly to regenerative medicine and cancer research, where they serve as recipients for allo- and xeno-grafts, with notable advantages over mouse models, including a longer lifespan and a much larger body size. Here we provide a concise review of the history and current status of the development of ID rabbits, as well as future perspectives of this new member in the animal model family.

scholarly journals Gene editing and CRISPR in the clinic: current and future perspectives

2020 ◽  
Vol 40 (4) ◽  
Author(s):  
Matthew P. Hirakawa ◽  
Raga Krishnakumar ◽  
Jerilyn A. Timlin ◽  
James P. Carney ◽  
Kimberly S. Butler
Keyword(s):  
Clinical Trials ◽  
Genome Editing ◽  
Dna Sequences ◽  
Gene Editing ◽  
Ex Vivo ◽  
Scientific Basis ◽  
Current Status ◽  
Zinc Finger Nucleases ◽  
Transcription Activator

Abstract Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases which require cell modification in vivo. However, in vivo use of CRISPR technologies can be confounded by problems such as off-target editing, inefficient or off-target delivery, and stimulation of counterproductive immune responses. Current research addressing these issues may provide new opportunities for use of CRISPR in the clinical space. In this review, we examine the current status and scientific basis of clinical trials featuring ZFNs, TALENs, and CRISPR-based genome editing, the known limitations of CRISPR use in humans, and the rapidly developing CRISPR engineering space that should lay the groundwork for further translation to clinical application.

CRISPR/Cas9 gene editing for genodermatoses: progress and perspectives

2019 ◽  
Vol 3 (3) ◽  
pp. 313-326 ◽  
Author(s):  
Gaetano Naso ◽  
Anastasia Petrova
Keyword(s):  
Gene Editing ◽  
Ex Vivo ◽  
Current Status ◽  
Transcription Activator ◽  
Base Editing ◽  
Novel Treatments ◽  
Ex Vivo Gene Therapy ◽  
Engineered Nucleases ◽  
Blistering Disease ◽  
Therapy Strategies

Abstract Genodermatoses constitute a clinically heterogeneous group of devastating genetic skin disorders. Currently, therapy options are largely limited to symptomatic treatments and although significant advances have been made in ex vivo gene therapy strategies, various limitations remain. However, the recent technical transformation of the genome editing field promises to overcome the hurdles associated with conventional gene addition approaches. In this review, we discuss the need for developing novel treatments and describe the current status of gene editing for genodermatoses, focusing on a severe blistering disease called epidermolysis bullosa (EB), for which significant progress has been made. Initial research utilized engineered nucleases such as transcription activator-like effector nucleases and meganucleases. However, over the last few years, clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) have upstaged older generation gene editing tools. We examine different strategies for CRISPR/Cas9 application that can be employed depending on the type and position of the mutation as well as the mode of its inheritance. Promising developments in the field of base editing opens new avenues for precise correction of single base substitutions, common in EB and other genodermatoses. We also address the potential limitations and challenges such as safety concerns and delivery efficiency. This review gives an insight into the future of gene editing technologies for genodermatoses.

scholarly journals IL-2 Signaling Axis Defects: How Many Faces?

2021 ◽  
Vol 9 ◽  
Author(s):  
Filippo Consonni ◽  
Claudio Favre ◽  
Eleonora Gambineri
Keyword(s):  
Current Knowledge ◽  
Interleukin 2 ◽  
Genetic Diagnosis ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Loss Of Function ◽  
Laboratory Findings ◽  
Forkhead Box ◽  
Signaling Axis ◽  
History Of

CD25, Signal transducer and activator of transcription 5B (STAT5B) and Forkhead box P3 (FOXP3) are critical mediators of Interleukin-2 (IL-2) signaling pathway in regulatory T cells (Tregs). CD25 (i.e., IL-2 Receptor α) binds with high affinity to IL-2, activating STAT5B-mediated signaling that eventually results in transcription of FOXP3, a master regulator of Treg function. Consequently, loss-of-function mutations in these proteins give rise to Treg disorders (i.e., Tregopathies) that clinically result in multiorgan autoimmunity. Immunodysregulation, Polyendocrinopathy Enteropathy X-linked (IPEX), due to mutations in FOXP3, has historically been the prototype of Tregopathies. This review describes current knowledge about defects in CD25, STAT5B, and FOXP3, highlighting that these disorders both share a common biological background and display comparable clinical features. However, specific phenotypes are associated with each of these syndromes, while certain laboratory findings could be helpful tools for clinicians, in order to achieve a prompt genetic diagnosis. Current treatment strategies will be outlined, keeping an eye on gene editing, an interesting therapeutic perspective that could definitely change the natural history of these disorders.

Role of Pharmacogenomics in Antiepileptic Drug Therapy: Current Status and Future Perspectives

2018 ◽  
Vol 23 (37) ◽  
pp. 5760-5765 ◽  
Author(s):  
Antonio Gambardella ◽  
Angelo Labate ◽  
Laura Mumoli ◽  
Iscia Lopes-Cendes ◽  
Fernando Cendes
Keyword(s):  
Drug Therapy ◽  
Antiepileptic Drug ◽  
Current Status ◽  
Future Perspectives ◽  
Antiepileptic Drug Therapy

Radio-localization of Non-Palpable Breast Lesions Under Ultrasonographic Guidance: Current Status and Future Perspectives

2017 ◽  
Vol 10 (3) ◽  
Author(s):  
Giulia Anna Follacchio ◽  
Francesco Monteleone ◽  
Maria Letizia Meggiorini ◽  
Maria Paola Nusiner ◽  
Carlo De Felice ◽  
...  
Keyword(s):  
Current Status ◽  
Breast Lesions ◽  
Future Perspectives ◽  
Radio Localization ◽  
Palpable Breast ◽  
Ultrasonographic Guidance

scholarly journals Artificial intelligence and colonoscopy: Current status and future perspectives

2019 ◽  
Vol 31 (4) ◽  
pp. 363-371 ◽  
Author(s):  
Shin‐ei Kudo ◽  
Yuichi Mori ◽  
Masashi Misawa ◽  
Kenichi Takeda ◽  
Toyoki Kudo ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Current Status ◽  
Future Perspectives
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