One-stop shop for human genome knock-in (KI) mouse/rat assessment services

Human genome KI mice and rats (or KI mice/rats), where the human genome is inserted into the animal’s intrinsic genome, are typically used in the assessment of candidate compounds with species differences and for deriving disease models. Axcelead offers a comprehensive range of solutions, from KI mouse/rat breeding through to IND-enabling non-clinical studies (pharmacology and toxicity) in KI mice/rats as well as conventional studies in monkeys, dogs and pigs.

Advantages of KI mice/rats

KI mice/rats are bred with the intrinsic mouse/rat gene deleted and replaced with the human genome, to allow assessment of drugs with species differences. KI mouse/rat assessment is recommended in the following scenarios.

〈New drug modalities〉

Given that toxicity studies of new modalities often fail to detect off-target toxicity, regulatory authorities now require on-target toxicity assessment on animals with demonstrated efficacy. Where efficacy has been tested via a pharmacological study of the drug discovery target on KI mice/rats carrying human genome, a toxicity study on the same KI mice/rats functions as on-target toxicity assessment.
KI mice/rats with long-chain gene arrangements in exon-intron structures are ideal for assessing efficacy and safety in oligonucleotide drug development. Axcelead is a leader in long-chain KI mouse creation.

〈Small molecule drugs〉

KI mouse/rat efficacy assessment can be used in cases where efficacy has not been demonstrated on any other species.

Axcelead offers a full range of solutions

Typical example
We tailor our services to your specific requirements. Contact us to find out more.

Key features of the Axcelead KI mouse/rat breeding program

★Hetero KI suitable for efficacy study available within just four months

We use CRISPR/Cas9 genome editing technology to accommodate a wide range of genetic backgrounds and for KI rat creation.

★Human genome replacement up to 40 kbp

Using homologous recombination of ES cells, it takes around eight months to obtain hetero KI, which also serves as long-chain KI for oligonucleotide drug assessment.

★Suitable for introducing mutations into genes with intrinsic mutations, such as in rare diseases, and also for KI of human genes with mutations introduced


Q : How successful is your KI animal breeding program?
A : The expert researchers at Axcelead boast many years of experience in KI animal breeding at Takeda Pharmaceuticals. In the most recent 67 consignment orders, we have successfully produced F0 generation KI across nearly all strains.

Q : Do you offer efficacy assessment on KI animals?
A : Yes we do. Many of our pharmacology researchers have been performing efficacy assessments on KI animals since their days at Takeda Pharmaceuticals, and boast considerable experience across a range of fields.

Q : Do you offer safety assessment on KI animals?
A : Yes, we have a number of studies currently in the planning stage. The recent shortage of cynomolgus monkeys has led to greater interest in safety assessment using KI animals, which is expected to become increasingly common.

Q : Can you perform IND-enabling studies using KI animals?
A : Yes we certainly can. At Axcelead, we have a number of leading safety experts with many years of experience , who will design an optimized IND-enabling study package to suit your specific requirements. Contact us to find out more.

Q : What are the costs associated with KI animal assessment?
A : For example, a GLP repeated dose toxicity study would typically require about 130 KI mice/rats,equivalent to around 40 cynomolgus monkeys. On the basis of animal numbers, the KI mouse/rat option will be far cheaper than using cynomolgus monkeys. Contact us to find out more.

Leave it to us !

Michiyasu Takeyama, PhD
Director, Translational Research
I joined Takeda Pharmaceuticals in 1991 after finishing a PhD in Engineering at the Osaka University Graduate School of Engineering. I have since worked exclusively on molecular biology research in areas such as transgenic animals and EST (expressed sequence tag) database analysis at the Tsukuba Research Institute, as well as early work on microarray analysis techniques. I was transferred to Axcelead Drug Discovery Partners from Takeda Pharmaceuticals when the company was founded in 2017. I served as Senior Biology Research Supervisor before taking on my current role in April 2020. We are proud of our technical achievements, forged in the demanding environment of Takeda Pharmaceuticals, and are keen to contribute to the world of drug discovery.

Hideo Fukui, PhD, DABT, DJSOT
Senior Director/Senior Consultant, Applied Regulatory Science
I joined Takeda Pharmaceuticals in 1989 after finishing a MS degree in Nutritional Biochemistry at the Nagoya University Graduate School of Bio agricultural Sciences. In 1994 I completed a PhD in Pharmacology at the Kyoto University Graduate School of Pharmaceutical Sciences. In 2000 I was appointed postdoctoral researcher at the Department of Medicine at Columbia University in the U.S. I have professional toxicologist accreditation from the American Board of Toxicology (ABT) in the U.S. and the Japanese Society of Toxicology (JSOT). I worked at Global Takeda as the lead on non-clinical safety assessments, primarily for therapeutic drugs in the gastroenterology domain, where my duties involved addressing a range of toxicity issues, liaising with regulatory authorities, and conducting due diligence on candidate compounds. I also served as President of the 48th Annual Meeting of the Japanese Society of Toxicology in Kobe in 2021.