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Knock-in Model Development Service

In the realm of rare disease drug and therapy development, knock-in models have emerged as a transformative tool, allowing scientists to unlock the secrets of genetic disorders and gain deeper insights into disease mechanisms. With years of industry experience, our company provides professional knock-in model development services. Through our dedication to scientific excellence, innovation, and collaborative partnerships, we strive to accelerate the discovery and development of novel therapeutics for a range of rare diseases.

Introduction to Knock-in Models

A knock-in model is a genetically modified organism, often a mouse, where a specific genetic sequence is inserted or substituted into an existing gene, mimicking disease-causing mutations or introducing targeted modifications. Knock-in models stand as the vanguard of genetic research, delving into the depths of perplexity and embracing the burstiness of molecular intricacies.   Through the modeling of human SNPs, genetic humanizations, and the radiant symphony of fluorescent reporter models, these remarkable tools propel us toward a deeper understanding of genetic complexity.

Fig.1 Easi-CRISPR for the knock-in model. (Miura, Hiromi, et al., 2018)Fig.1 Easi-CRISPR for the knock-in model. (Miura, Hiromi, et al., 2018)

Like cosmic navigators charting unexplored territories, researchers harness the power of knockin mice to recapitulate human diseases, assess the efficacy of compounds, unravel the mysteries of promoter activity, unveil the enigmatic expressions of mutant proteins, trace the intricate pathways of cell trafficking, replace genes with reporter genes, and embark on audacious humanization endeavors.

Strategies of Knock-in Model Development

Knock-in models employ diverse strategies to introduce genetic modifications and mimic disease-associated mutations. By utilizing these strategies, researchers can gain a comprehensive understanding of gene function and the impact of specific mutations on disease progression. The following table presents a comparative analysis of three innovative strategies devised for the knockin model:

Table 1 Comparison of knock-in strategies. (Miura, Hiromi, et al., 2018)

Feature Easi-CRISPR Insertion via HR (homologous recombination) of dsDNA donor MMEJ (microhomology-mediated end joining) using dsDNA donor (PITCh, precise integration into the target chromosome)
Insert size Up to ~1.5 kb (refs. 8,9,38) Up to 11 kb (refs. 31,33,43–47) Up to 4–5 kb (ref. 32)
Length of homology arms 55–105 bases Typically, ~0.5–2 kb (up to ~7.5 kb) ~40 bases
Difficulty of donor DNA construction Easy Difficult in most cases Easy
Knock-in efficiency 8.5–100% (typically 30–60%) 0–50% (typically ~10% or less) 12.0% (without Exo1), 35.7% (with Exo1)

Our Services

As a leading company in the field of biological research, our commitment to advancing knock-in models is unwavering. We employ cutting-edge gene-editing technologies to create reliable knock-in models, and used the models for drug safety evaluation and pharmacokinetics studies. Our team of experienced scientists works tirelessly to collaborate with researchers globally, offering tailored solutions to meet their specific research needs.

  • Animal Species for Model Development

-Mouse
-Rat
-Rabbit

-Pig
-Dog

-Monkey
-Cat

-Zebrafish
-Other

  • Methods of Knock-in Model Development

-Homologous Recombination in ES cells
-Genome Editing Nucleases

-Random Transgenesis
-Targeted Transgenesis

  • Types of Knock-in Model Development
    Constitutive / Conventional / Whole-body Knock-in Models:
    By introducing point mutations into the homology arms or targeting vector, we can incorporate the desired mutations into the target gene. These mutations will be stably expressed under the control of the wildtype gene regulatory elements.
    Reporter Knock-in Models:
    Insert a reporter gene at the end or beginning of the coding sequence, creating a fusion protein. This allows for monitoring gene expression at the transcriptional or translational level and studying protein localization/trafficking.
    Quick (Rosa26 and Hprt) Knock-in Models:
    We offer knock-in mouse and rat models with safe and targeted insertion of transgenes into the HPRT and Rosa26 loci.
    Humanized Knock-in Models:
    Humanized genetically engineered mouse models are created by replacing the mouse endogenous gene with its corresponding human ortholog.
    Point Nutation Models:
    Knock-in of the target gene is achieved by constructing point mutation models.

Why Choose Us?

Genetically Engineering Model Development Services

With our extensive expertise in researching and developing therapies for rare diseases, our company offers comprehensive services to leading and emerging biopharmaceutical firms and scientific research institutions. We specialize in the development of knock-in models for rare diseases, utilizing our advanced platform. We take pride in providing top-notch services and delivering high-quality products that meet the unique requirements of our customers. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

Reference

  • Miura, Hiromi, et al. "Easi-CRISPR for creating knock-in and conditional knockout mouse models using long ssDNA donors." Nature protocols 13.1 (2018): 195-215.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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