Neuroscience Research Using Non-human Primate Models and Genome Editing

Abstract

The common marmoset (Callithrix jacchus) is a small New World non-human primate indigenous to northeastern Brazil. This species has been attracting the attention of biomedical researchers and neuroscientists for its ease of handling and colony maintenance, unique behavioral characteristics, and several human-like traits, such as enriched social vocal communication and strong relationships between parents and offspring. Its high reproductive efficiency makes it particularly amenable for use in the development of transgenic and genome editing technologies in a non-human primate model. Our group has recently generated transgenic marmosets with germ line transmission, opening new avenues in primate research.In this chapter, we describe recent advances in neuroscience and disease research using common marmosets, and we outline potential uses of genome editing in non-human primates toward the development of knock-in/knock-out marmosets.

Induced pluripotent stem cells and genome editing technology as therapeutic strategies for Duchenne muscular dystrophy

“…Functional dystrophin protein in skeletal and heart muscle was partially recovered following the deletion of exon 23, as shown by improvement of muscle strength. 50 Amoasii et al 51 injected adeno-associated virus (AAV) vectors carrying the CRIPSR component either intramuscularly or intravenously into DMD dog models. After 6 to 8 weeks, they found significant improvement in muscle, particularly cardiomyocytes.…”

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

“…Tools such as ZFNS (zinc finger nucleases), TALENS (transcription activatorlike effector nucleases), and CRISPR (clustered regularly interspaced short palindromic repeats, with RNA-guided nucleases such as Cas9) have made possible this once out-of-reach goal ( Park & Silva, 2019 ). This has led to calls for the creation of lines of GA NHPS and arguments for their necessity to biomedical science ( Jennings et al, 2016 ; Scaduto, 2016 ; Kishi & Okano, 2017 ). Germline transmission in common marmosets was first reported in 2009 ( Sasaki et al, 2009 ), raising the possibility of establishing colonies of GA NHPS for use in biomedical research.…”

“…In addition to their greater fecundity and faster maturity than macaque species, the small size of common marmosets (300–400 g), their relatively ease of handling and the fact they do not carry herpes-B virus, has made them attractive species for gene editing research in Japan and the USA ( Schatten & Mitalipov, 2009 ; Kishi & Okano, 2017 ; Anestidou & Johnson, 2019 ; Cyranoski, 2019 ). Demand for marmosets is now so high in the USA, there is a national shortage, with some calling for sourcing of wild animals from their native Brazil ( Servick, 2018 ).…”

“…Therefore, the animal subjects can be expected to undergo administration of drugs by intended clinical routes, physiologic sampling and behavioral testing. Those used in basic neurophysiology, or modeling of brain disorders, may be expected to experience the neuroimaging, surgical implantation of recording/stimulation devices, cognitive testing, food/fluid restriction, prolonged restraint and social separation currently used in most NHP experiments in the awake, behaving state, and to be utilized over a period of many years (Prescott et al, 2010;Kishi & Okano, 2017). In the UK, such long-term protocols have a prospective severity classification of 'severe' .…”

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

“…Macaques and marmosets are often chosen as model animals, because these species exhibit ‘highly structured communication patters’. Therefore, these very social animals are supposed to ‘offer a valuable new route for assessing the role of genes involved in social interaction’ (Kishi and Okano, 2017). Recently, researchers have created five cynomolgus monkeys ( Macaca fascicularis ) with ‘knocked out’ BMAL1 genes.…”