Target validation and qualification could help assess confidence in a drug throughout the development process. Creative Biolabs owns a range of genetically engineered rodent/nonhuman primate (NHP) models to offer high-quality target validation and qualification services for psychotropic drug development.
Genetically Modified Models for Psychiatric Disorders
Psychiatric disorders are a prevalent global health problem. Due to this high prevalence and the substantial societal costs, it is important to understand the underlying mechanisms to facilitate the development of new effective treatments. Our current knowledge in the etiology and the pathophysiology of psychiatric disorders owes a great debt to the research undertaken with animals. Given the strict ethical limitations to human experimentation, animal models are the best alternative to tackle the major challenges in this field.
Due to the advent of recombinant DNA technologies in the early 1980s, genetically modified rodent models have significantly contributed to the study of psychiatric disorders. However, despite significant advancements, many challenges remain after unsuccessful drug development based on rodent models. Given the phylogenetic gap between humans and rodents, which translates to considerable differences in physiology and behavioral profiles, NHPs stand as the most appropriate animal models for several psychiatric symptoms. Considering the close evolutionary relationship and similarity of brain structures in NHPs and humans, NHPs will be indispensable in the study of psychiatric disorders.
Fig.1 CRISPR/Cas9 workflow. (Baker, 2020)
Genetic Approaches Employed in Rodent/NHP Models
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Viral-based genetic approaches
Lentiviral vectors that can infect both dividing and non-dividing cells have been widely used to introduce transgenes or gene knockdown. Many rodent models have been successfully produced using lentiviral vectors. While for NHPs, taking advantage of the high efficiency of lentiviral infection, genetic engineering has been done in marmoset (Callithrix jacchus). Researchers have used lentiviral-based methods to produce transgenic marmosets carrying GFP transgenes. Importantly, they obtained a second-generation carrying the transgene, which indicates the reliability of transgenic monkeys as animal models.
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Precision genome-editing based genetic approaches
The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system and TALEN genome-editing methods have emerged as powerful tools, making genetic engineering in rodents and NHPs feasible and relatively easy. One advantage of CRISPR over traditional gene knockout models is its ability to edit many genes simultaneously, which is particularly necessary considering the complex polygenetic nature of psychiatric disorders.
Given the availability of lentiviral transduction methods and CRISPR/Cas system, a series of transgenic rodents and NHPs, including but not limited to autism, schizophrenia, addiction, anxiety and depression, have been developed to model various psychiatric disorders. With proven experience in drug development, Creative Biolabs is an ideal company to entrust with your business. We offer accurate and effective solutions for researchers in target validation and qualification. Please contact us for more information about our rodent/NHP models for target validation and qualification.
References
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Qiu, Z.; Li, X. Non-human primate models for brain disorders–towards genetic manipulations via innovative technology. Neuroscience bulletin. 2017, 33(2):247-50. Distributed under Open Access license CC BY 4.0, without modification.
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Baker, M.; et al. Rodent models for psychiatric disorders: problems and promises. Laboratory Animal Research. 2020, 36:1-0. Distributed under Open Access license CC BY 4.0, without modification.
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