Model generation, gene targeting strategy and model validation
1. Could you share your comprehensive humanized model list?
Yes. Biocytogen has the most comprehensive list of humanized immune checkpoint and humanized cytokine (receptor) mouse models on the market, and more than 100 new models are under development!
If the models that you are interested in are not on our public list, they are most likely being generated internally. Please contact us and we can update you on our progress and possibly share with you the available data. Otherwise, we can generate a specific model for you with our extensive experience in developing humanized mouse models.
We are open to opportunities for co-development and co-validation of new models to share cost and to speed up the model generation process. Please contact us for details.
2. Can you do new model generation?
Yes. Biocytogen has been providing gene editing services for over a decade! We can do rat and mouse gene modification and cell line modification. In 2018, we delivered >1,500 projects for our clients around the world.
3. What is the targeting strategy of your humanized model?
Usually Biocytogen does NOT disclose detailed targeting strategy information of specific models. Generally, in a typical humanized model, the coding region of extracellular domain of murine immune checkpoint is replaced by its human counterpart. Transmembrane and intracellular domains remain murine to keep intracellular signaling transduction cascades intact. Since the promoter region is from murine, in theory, the expression level and pattern of the humanized gene shall be very similar to the mouse gene.
4. How many animals in each group/arm would Biocytogen recommend for an in vivo efficacy study?
Usually, we recommend 8-12 animals in each group/arm. 6 is the minimum number of animals in a group/arm.
5. What validation data do you have?
Our standard validation assays are enumerated as follows: RT-PCR (reverse transcriptase polymerase chain reaction) and FACS (flow cytometry and fluorescence-activated cell sorting) are used to evaluate human mRNA/protein expression; immune cell profiling and blood test are performed to examine any abnormalities after genetic modification; in vivo studies of human antibodies targeting humanized receptors (or binding partners) of interest are executed to assess antibody efficacies. Toxicity evaluation of human antibodies and in vitro functional assays (killing, activation, etc.) have been performed for several models. Biocytogen welcomes any suggestions and comments that help us better validate the models.
6. Can a client request some splenocytes for a pilot study to validate Biocytogen’s model before a big purchase?
Yes. Biocytogen can provide frozen splenocytes and a few animals for a pilot study, and we can also perform binding assays to test if a client’s antibody can bind with a humanized target of interest.
Our Facilities: Animal breeding and shipment
1. Where is your animal breeding facility? Could you give a brief introduction?
Biocytogen’s animal breeding facility is operated under Biocytogen Jiangsu Co., Ltd, located in in Haimen city, Jiangsu province of China, is about 78 miles North of Shanghai. The facility, approximately 160,000 ft2(15,000 m2), was established in 2015 and received AAALAC accreditation in 2016.
2. Can Biocytogen ship animals to other countries/regions outside of mainland China?
Yes. We have worked closely with World Courier Inc. for years to transport animals from China to other countries/ regions. Our animals have been successfully delivered worldwide including Asia, Europe and North America. Clients only need to provide required shipping information to us and we can initiate shipment preparation.
3. How long will the lead time take from ordering to receiving the animals?
In general, once we have all the paperwork in place and collected the PO, it takes about 4 weeks to receive the animals. Because some strains are in high demand and we strongly encourage our clients to give us an advance notice to reserve required animals as early as possible to avoid unnecessary waiting time.
4. What is the difference between Biocytogen’s US site and China site?
Both sites provide extensive and reliable services. Some of our US clients prefer the US site (Wakefield, MA; 30 driving distance from Cambridge, MA) for convenient sample transfers and local communications.
Preclinical study plan and initiation
1. What constitutes a pre-clinical in vivo study at Biocytogen and what does the cost per mouse include?
A standard in vivo study includes dosing, tumor inoculation, randomization, weighting mice, interim reports on tumor volume and body weight measurements and a detailed final report.
Biocytogen usually inoculate an additional 25%-40% animals to reduce tumor volume variations. Only the number of animals in the designed studies are charged, and we do NOT charge for the 25-40% animals used in the additional inoculations.
Additional charges shall apply to other services such as tumor/organ/tissue collections, and customers are responsible for costs of transferring samples and/or compounds.
Our business model and service costs
1. What is your business model?
We can either sell the animals, license the animal models or perform in vitro/in vivo/ex vivo experimental studies using our platforms. If you would like to expand animal models in your facility by self-breeding, a license is required.
2. What are the costs of ordering mice, licensing a model, and conducting an in vivo efficacy study?
It depends on multiple factors, such as the size of an order, the plan of study and the type of strain. Please contact us for further info.