Primate Organoids and Gene-Editing Technologies toward Next-Generation Biomedical Research

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.

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Against the use and publication of contemporary unethical research: the case of Chinese transplant research

Journal of Medical Ethics ◽

10.1136/medethics-2019-106044 ◽

2020 ◽

Vol 46 (10) ◽

pp. 678-684 ◽

Cited By ~ 1

Author(s):

Wendy C Higgins ◽

Wendy A Rogers ◽

Angela Ballantyne ◽

Wendy Lipworth

Keyword(s):

Biomedical Research ◽

Gene Editing ◽

Large Body ◽

Three Dimensions ◽

Unethical Practices ◽

Unethical Research

Recent calls for retraction of a large body of Chinese transplant research and of Dr Jiankui He’s gene editing research has led to renewed interest in the question of publication, retraction and use of unethical biomedical research. In Part 1 of this paper, we briefly review the now well-established consequentialist and deontological arguments for and against the use of unethical research. We argue that, while there are potentially compelling justifications for use under some circumstances, these justifications fail when unethical practices are ongoing—as in the case of research involving transplantations in which organs have been procured unethically from executed prisoners. Use of such research displays a lack of respect and concern for the victims and undermines efforts to deter unethical practices. Such use also creates moral taint and renders those who use the research complicit in continuing harm. In Part 2, we distinguish three dimensions of ‘non-use’ of unethical research: non-use of published unethical research, non-publication, and retraction and argue that all three types of non-use should be upheld in the case of Chinese transplant research. Publishers have responsibilities to not publish contemporary unethical biomedical research, and where this has occurred, to retract publications. Failure to retract the papers implicitly condones the research, while uptake of the research through citations rewards researchers and ongoing circulation of the data in the literature facilitates subsequent use by researchers, policymakers and clinicians.

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Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells

Journal of Experimental Medicine ◽

10.1084/jem.20171626 ◽

2018 ◽

Vol 215 (3) ◽

pp. 985-997 ◽

Cited By ~ 89

Author(s):

Akiko Seki ◽

Sascha Rutz

Keyword(s):

T Cells ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Gene Editing ◽

Target Gene ◽

Gene Knockout ◽

Great Promise ◽

Next Generation ◽

Primary Mouse

CRISPR (clustered, regularly interspaced, short palindromic repeats)/Cas9 (CRISPR-associated protein 9) has become the tool of choice for generating gene knockouts across a variety of species. The ability for efficient gene editing in primary T cells not only represents a valuable research tool to study gene function but also holds great promise for T cell–based immunotherapies, such as next-generation chimeric antigen receptor (CAR) T cells. Previous attempts to apply CRIPSR/Cas9 for gene editing in primary T cells have resulted in highly variable knockout efficiency and required T cell receptor (TCR) stimulation, thus largely precluding the study of genes involved in T cell activation or differentiation. Here, we describe an optimized approach for Cas9/RNP transfection of primary mouse and human T cells without TCR stimulation that results in near complete loss of target gene expression at the population level, mitigating the need for selection. We believe that this method will greatly extend the feasibly of target gene discovery and validation in primary T cells and simplify the gene editing process for next-generation immunotherapies.

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Ethical and Welfare Implications of Genetically Altered Non-Human Primates for Biomedical Research

Journal of Applied Animal Ethics Research ◽

10.1163/25889567-bja10002 ◽

2020 ◽

pp. 1-26

Author(s):

Mark J. Prescott

Keyword(s):

Biomedical Research ◽

Gene Editing ◽

Ethical Issues ◽

Neurological Diseases ◽

Therapeutic Interventions ◽

Large Numbers ◽

The Usa ◽

Welfare Implications ◽

Models Of Disease ◽

Human Primate

Abstract Breakthroughs in gene editing technologies have made it feasible to create genetically altered (GA) non-human primate (NHP) models of disease. This area of research is accelerating, particularly in China, Japan and the USA, and could lead to an increase in NHP use globally. The hope is that genetic models in animal species closely related to humans will significantly improve understanding of neurological diseases and validation of potential therapeutic interventions, for which there is a dire need. However, the creation and use of GA NHPs raises serious animal welfare and ethical issues, which are highlighted here. It represents a step change in how these highly sentient animals are used in biomedical research, because of the large numbers required, inherent wastage and the sum of the harms caused to the animals involved. There is little evidence of these important issues being addressed alongside the rapidly advancing science. We are still learning about how gene editing tools work in NHPs, and significant added scientific and medical benefit from GA NHP models has yet to be demonstrated. Together, this suggests that current regulatory and review frameworks, in some jurisdictions at least, are not adequately equipped to deal with this emerging, complex area of NHP use.

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