Advancing Personalized Medicine Through Rapid Phenotyping

Genomic medicine gap: the questionable alleles in everyone's genome

Genomic medicine is revealing a big gap in medical knowledge. Whole genome data reveals each person has about 400-500 sequence variants creating missense or indel in the coding regions of their genome. With estimates as high as 25% of the genes in the human genome being involved in disease biology, any one individual harbors about 100 codon-changing issues in their important “disease” genes.  Surprisingly, frameshifting indels account for 6.7% of these variant lesions. (PMC5282828).  As a result, a significant number of questionable alleles are part of the background of anyone’s personal genome. How does the physician and clinical geneticist make sense of this noise in the system when trying to determine:

Is the gene mutation seen in my patient Benign or Pathogenic?

Phenotype Profiling in Animal Models

fish and worm

CRISPR technology now allows us to insert the same mutations seen in disease genes into the same homologous gene present in animal models (PMID:28677007). This allows one to fully characterize the phenotypic effect of a disease mutant allele in a well controlled system. Traditionally, this has been done in mice models, but is highly expensive.  Knudra Transgenics in partnership with NemaMetrix is developing a platform for robust production and analysis of clinical variants. The homologous mutation is installed in an animal model and the effect on physiology is measured. Two powerful models that can be manipulated easily in fluidics paradigms are C. elegans and zebrafish.  When a clinical variant is installed in fish, the researcher can examine if the phenotypic effect is conserved with man.  Although the worm does not have the same physiological similarity as fish, the installation of clinical variant in the worm frequently has functional consequence if the gene mutation installed is truly pathogenic. The result is a multi-animal system for discovery of disease biology. Because both animal models thrive in liquid formats, It becomes easy to rapidly screen compounds for therapeutic effects.  Microfluidics systems have recently be introduced by NemaMetrix (ScreenChip) to enable rapid and quantitative measure of phenotype in C. elegans. By combining the ScreenChip system with the fast production of transgenics at Knudra, researchers can now access to a rapid phenotyping system detecting the presences of pathogenicity in clinical variants of uncertain significance. Mutation-specific animal models can be made and tested in a few weeks, instead of the years it takes with traditional animal models.  The capacity for fast assessment may allow decisions on treatment options to be made in a time frame where a positive impact can be quite high.  Ultimately a faster decision on how to devise a treatment will enable care providers to improve patent outcome and save lives.

Knudra is Attending ZDM10 - Zebrafish Disease Models in its 10th Year

The ZDM10 is a premier international meeting of zebrafish researchers who hold a focus on disease modeling.

Knudra is showcasing its Verified Clutch services which zebrafish researchers can use to build humanized animal models.  Point mutations observed in humans and suspected of causing pathogenicity can be installed into the fish genome.  The result is a powerful platform for discovery of disease biology. 

Come see us at vendor booth #13 to find out how our various transgenesis service can be deployed to meet your research needs.

Oxford Genome Editing and Transgenics - Knudra Presents Various Methods of Genome Engineering

Join us at the Genome Editing & Advances in Transgenic Technology USA Congress in Boston, MA, May 10-11.  Don’t miss our presentation, "Humanized Animal Models Customized for Discovery of Disease Biology", at 2:50pm on May 10th. Come find out how we build designer genomes for our clients.  Learn about our methods to create precision deletions with oligonucleote donor homology ("trueDEL nulls"), make fluorescent protein insertions via PCR product ("KRISPR-sdm"), and how to use transgenics platforms to discover pathogenicity in clinical variants ("RediMODEL"). Please contact us for attendance discounts. 

RediMODEL-ScreenChip at ACSB Meeting

In continuing collaboration with NemaMetrix, Knudra Transgenics showcases the integrated platform at ACSB meeting.

ACSB is a premier meeting for revealing the latest details in various fields like cancer biology to understanding the latest imaging techniques. At ACSB, we will showcase Knudra's capacity to build animal models and how this is evolving towards providing animal model kits for rapid discovery of biology on your favorite gene.  Come see how RediMODEL and ScreenChip systems can be used to Accelerate your Science.

CRISPR/Cas9 Technology Licensed from ERS

DUBLIN, Ireland, and SALT LAKE CITY, Utah, November 2nd, 2016 (business-wire)1 - ERS Genomics Ltd and Knudra Transgenics, a leader in model-organism bioengineering, announced today a non-exclusive license agreement which provides Knudra with worldwide access to ERS’ CRISPR-Cas9 genome editing intellectual property for use in engineering of model organisms. ERS Genomics holds rights to the foundational CRISPR-Cas9 patent portfolio from Dr. Emmanuelle Charpentier, an inventor of the breakthrough gene-editing technology.

Under the license Knudra scientists will use CRISPR technology to engineer C. elegans (commonly known as nematodes or roundworms) and D. rerio (commonly known as zebrafish) to build custom models and develop related products for their customers. Both organisms are used widely as powerful platforms for medical discovery and drug development in both basic research and the pharmaceutical and biotechnology industry.

“Knudra is a young and energetic group of highly-skilled gene editing experts and we are very pleased to provide them with access to the most powerful genome engineering technology available. We believe Knudra is a great example of how a smaller company, dedicated to building platforms for medical discovery, can benefit from use of this exciting new technology. It is very important to ERS Genomics to provide broad access to the foundational technology and we are focused on enabling as many of these companies as possible to harness CRISPR-Cas9 in multiple areas,” said Eric Rhodes, CEO of ERS Genomics.

“CRISPR-Cas9 is a very powerful tool and we are excited to have gained access to this technology through ERS Genomics. We fully expect to see an enhancement to our current genome editing capabilities,” said Dr. Chris Hopkins, CSO of Knudra. “We look forward to applying CRISPR technology in our TAVASERV Transgenesis Services. We expect the resulting integration will provide significant benefits to our customers’ research needs,” commented Dr. Trisha Brock, CEO of Knudra.

Dr. Emmanuelle Charpentier’s research unveiled the key components and mechanisms of the CRISPR-Cas9 system, leading to the landmark publication with Jennifer Doudna,( Jinek, Chylinski et al., 2012 )2, which laid the foundation for the use of CRISPR-Cas9 as a highly versatile and precise genome editing tool.

About ERS Genomics. ERS Genomics was formed to provide broad access to the foundational CRISPR-Cas9 intellectual property held by Dr. Emmanuelle Charpentier. Non-exclusive licenses are available for research and sale of products and services across multiple fields including: research tools, kits, reagents; discovery of novel targets for therapeutic intervention; cell lines for discovery and screening of novel drug candidates; GMP production of healthcare products; production of industrial materials such as enzymes, biofuels and chemicals; and synthetic biology. For additional information please visit

About Knudra. Knudra Transgenics was formed in late 2009. Since the first client project completed in early 2010, the Knudra team has been supplying researchers and private entities custom-built transgenics. Starting first in C elegans then expanding into zebrafish, Knudra has gained the experience to efficiently get clients the transgenics they need. The Knudra Team has a combined over 30 years of experience in making transgenic organisms. Knudra uses the latest advances in genome engineering to build powerful platforms of medical discovery. Knudra has transformed its passion for genome engineering into a first-in-kind contract research service. CRISPR/Cas9 expands Knudra's service capacity as mentioned in Transgenic News,3 PharmaLetter 4 and Genomeweb.5 With licensed access to CRISPR/Cas9, Knudra will be introducing RediModel as a system of humanized animal models in an easy-to-use kit format, as profiled by Outsorucing-Pharma.6

1. ERS Genomics and Knudra Transgenics Sign License Agreement on CRISPR-Cas9 Genome Editing Patents for Model-Organisms.

2. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

3. Knudra in Deal to Use CRISPR-Cas9 Gene Editing.

4. Knudra in deal to use ERS Genomics’ CRISPR-Cas9 gene editing IP.

5. ERS Genomics Licenses CRISPR/Cas9 to Knudra Transgenics.

6. Knudra Transgenics licenses CRISPR-Cas9 tech to build custom models.