scholarly journals Genome editing in large animals: current status and future prospects

2019 ◽  
Vol 6 (3) ◽  
pp. 402-420 ◽  
Author(s):  
Jianguo Zhao ◽  
Liangxue Lai ◽  
Weizhi Ji ◽  
Qi Zhou
Keyword(s):  
Regenerative Medicine ◽  
Genome Editing ◽  
Biomedical Research ◽  
Human Disease ◽  
Gene Editing ◽  
Disease Modeling ◽  
Current Status ◽  
Future Prospects ◽  
Recent Advances ◽  
Large Animals

AbstractLarge animals (non-human primates, livestock and dogs) are playing important roles in biomedical research, and large livestock animals serve as important sources of meat and milk. The recently developed programmable DNA nucleases have revolutionized the generation of gene-modified large animals that are used for biological and biomedical research. In this review, we briefly introduce the recent advances in nuclease-meditated gene editing tools, and we outline these editing tools’ applications in human disease modeling, regenerative medicine and agriculture. Additionally, we provide perspectives regarding the challenges and prospects of the new genome editing technology.

scholarly journals Targeted Gene Editing in Porcine Spermatogonia

2021 ◽  
Vol 11 ◽  
Author(s):  
Dennis Webster ◽  
Alla Bondareva ◽  
Staci Solin ◽  
Taylor Goldsmith ◽  
Lin Su ◽  
...  
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Human Disease ◽  
Gene Editing ◽  
Disease Modeling ◽  
Germline Stem Cell ◽  
End Joining ◽  
Homology Directed Repair ◽  
Pig Genome ◽  
Targeted Gene Editing

To study the pathophysiology of human diseases, develop innovative treatments, and refine approaches for regenerative medicine require appropriate preclinical models. Pigs share physiologic and anatomic characteristics with humans and are genetically more similar to humans than are mice. Genetically modified pigs are essential where rodent models do not mimic the human disease phenotype. The male germline stem cell or spermatogonial stem cell (SSC) is unique; it is the only cell type in an adult male that divides and contributes genes to future generations, making it an ideal target for genetic modification. Here we report that CRISPR/Cas9 ribonucleoprotein (RNP)-mediated gene editing in porcine spermatogonia that include SSCs is significantly more efficient than previously reported editing with TALENs and allows precise gene editing by homology directed repair (HDR). We also established homology-mediated end joining (HMEJ) as a second approach to targeted gene editing to enable introduction of larger transgenes and/or humanizing parts of the pig genome for disease modeling or regenerative medicine. In summary, the approaches established in the current study result in efficient targeted genome editing in porcine germ cells for precise replication of human disease alleles.

scholarly journals iPSC technology-based regenerative medicine for kidney diseases

2021 ◽  
Author(s):  
Kenji Osafune
Keyword(s):  
Regenerative Medicine ◽  
Cell Therapy ◽  
Kidney Development ◽  
Disease Modeling ◽  
Kidney Diseases ◽  
Collecting Duct ◽  
Current Status ◽  
Renal Tubules ◽  
Discovery Research ◽  
Drug Discovery Research

AbstractWith few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct organoids. Furthermore, human kidney tissues can be generated from these hiPSC-derived progenitors, in which NPC-derived glomeruli and renal tubules and UB-derived collecting ducts are interconnected. The induced kidney tissues are further vascularized when transplanted into immunodeficient mice. In addition to the kidney reconstruction for use in transplantation, it has been demonstrated that cell therapy using hiPSC-derived NPCs ameliorates acute kidney injury (AKI) in mice. Disease modeling and drug discovery research using disease-specific hiPSCs has also been vigorously conducted for intractable kidney disorders, such as autosomal dominant polycystic kidney disease (ADPKD). In an attempt to address the complications associated with kidney diseases, hiPSC-derived erythropoietin (EPO)-producing cells were successfully generated to discover drugs and develop cell therapy for renal anemia. This review summarizes the current status and future perspectives of developmental biology of kidney and iPSC technology-based regenerative medicine for kidney diseases.

scholarly journals CRISPR Pioneers Win 2020 Nobel Prize for Chemistry

2020 ◽  
Author(s):  
Dariush D. FARHUD ◽  
Marjan ZARIF-YEGANEH
Keyword(s):  
Clinical Practice ◽  
Human Genome ◽  
Genome Editing ◽  
Nobel Prize ◽  
Gene Editing ◽  
High Accuracy ◽  
Recent Advances ◽  
Programmable Nucleases

Over the last few years, the development of genome editing has revolutionized research on the human genome. Recent advances in developing programmable nucleases, such as meganucleases, ZFNs, TALENs and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas, has greatly expedited the progress of gene editing from concept to clinical practice. The CRISPR has advantages over other nuclease-based genome editing tools due to its high accuracy, efficiency, and strong specificity. Eight years after CRISPR application for human genome edition by Emmanuelle Charpentier and Jennifer A. Doudna, the 2020 Nobel Prize in Chemistry has been jointly given to them for development of CRISPR-Cas9 gene editing, allows scientists to precisely cut and edit of DNA.

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.

scholarly journals Protoplasts: From Isolation to CRISPR/Cas Genome Editing Application

2021 ◽  
Vol 3 ◽  
Author(s):  
Jin-Jun Yue ◽  
Jin-Ling Yuan ◽  
Fu-Hui Wu ◽  
Yu-Hsuan Yuan ◽  
Qiao-Wei Cheng ◽  
...  
Keyword(s):  
Genome Editing ◽  
Gene Editing ◽  
Protoplast Regeneration ◽  
Self Incompatibility ◽  
Future Prospects ◽  
Juvenile Period ◽  
Free Gene ◽  
Protoplast Transfection ◽  
Cas Proteins

In the clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR associated protein (Cas) system, protoplasts are not only useful for rapidly validating the mutagenesis efficiency of various RNA-guided endonucleases, promoters, sgRNA designs, or Cas proteins, but can also be a platform for DNA-free gene editing. To date, the latter approach has been applied to numerous crops, particularly those with complex genomes, a long juvenile period, a tendency for heterosis, and/or self-incompatibility. Protoplast regeneration is thus a key step in DNA-free gene editing. In this report, we review the history and some future prospects for protoplast technology, including protoplast transfection, transformation, fusion, regeneration, and current protoplast applications in CRISPR/Cas-based breeding.

scholarly journals Modeling human neurodevelopmental diseases with brain organoids

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoxiang Lu ◽  
Jiajie Yang ◽  
Yangfei Xiang
Keyword(s):  
Stem Cells ◽  
Human Brain ◽  
Pluripotent Stem Cells ◽  
Neurodevelopmental Disorders ◽  
Human Disease ◽  
Gene Editing ◽  
Disease Modeling ◽  
Developmental Abnormalities ◽  
The Past ◽  
Underlying Mechanisms

AbstractStudying the etiology of human neurodevelopmental diseases has long been a challenging task due to the brain’s complexity and its limited accessibility. Human pluripotent stem cells (hPSCs)-derived brain organoids are capable of recapitulating various features and functionalities of the human brain, allowing the investigation of intricate pathogenesis of developmental abnormalities. Over the past years, brain organoids have facilitated identifying disease-associated phenotypes and underlying mechanisms for human neurodevelopmental diseases. Integrating with more cutting-edge technologies, particularly gene editing, brain organoids further empower human disease modeling. Here, we review the latest progress in modeling human neurodevelopmental disorders with brain organoids.

scholarly journals Genome Editing Animals and the Promise of Control in a (Post-) Anthropocentric World

2019 ◽  
Vol 26 (1) ◽  
pp. 3-25
Author(s):  
Rosine Kelz
Keyword(s):  
Genome Editing ◽  
Ecosystem Management ◽  
Biomedical Research ◽  
Gene Editing ◽  
Germ Line ◽  
Life Sciences ◽  
Modern Life ◽  
Daily Lives ◽  
The Public ◽  
Microbiological Research

Gene editing tools are ‘revolutionizing’ microbiological research. Much of the public debate focuses on the possibility of human germ line applications. The use of genome editing to alter non-human animals, however, will have more immediate impacts on our daily lives. Genome edited animals are used for basic biological and biomedical research and could soon play a role in the livestock industry and ecosystem management. Genome editing thus provides an occasion to rethink societal narratives about the relationships between humans and other animals. Even though the technique can be easily incorporated as an example into a conventional storyline about the development of the modern life sciences as striving for control over nature, it can also help to highlight the anthropocentric biases expressed in these narratives and demonstrate the continuities between humans and other animals.

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