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Project Description

Please note that we are a research service provider, not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Humanized Animal Model Development Services

Humanized animal models are extremely powerful in vivo platforms in ophthalmic research, enabling accurate disease modeling and therapy development. Protheragen specializes in the development of advanced humanized animal models for therapeutics development for ophthalmic disorders.

Introduction to Humanized Animal Models

Humanized animal models are creatures which either genetically or biologically altered to include human features such as genes, cells, or immune systems for the purpose of simulating human functional or disease processes more accurately. Such models serve as a link between conventional animal research and human clinical trials as they offer a more appropriate model for animal research, drug interactions, and medical therapeutics for humans. There are numerous ways to accomplish scientific humanization, such as:

Genetic Humanization: Introducing human genes into the animal genome to express human proteins or receptors.
Cell or Tissue Humanization: Transplanting human cells or tissues into animals, such as human corneal endothelial cells into rabbit or feline models.
Immune System Humanization: Reconstituting the animal's immune system with human immune cells to study human-specific immune responses.

Different methods for constructing humanized mice.

Fig.1 Different construction methods of humanized mice. (Chen J., et al., 2022)

Application of Humanized Animal Models in Ophthalmic Diseases

With respect to eye diseases, humanized animal models represent a vital aspect of the therapeutics advancement process. These models allow the investigation of complex processes related to eye diseases including, but not limited to, age-related macular degeneration, diabetic retinopathy, and glaucoma. Their human-like ocular settings allow for the discovery of new therapeutic targets and the assessment of promising therapeutic approaches.

Table 1. Immunization responses in mice engrafted with a human immune system. (Ye W., et al., 2022)

Use	Mouse strain	Engrafted tissue	Component	Comments
Therapeutic vaccine	NOG	CB CD34⁺	HER2 peptide	Production of anti-HER2 IgM
	NSG	CB CD34⁺	Human immunodeficiency virus type 1 (HIV-1)	Increased IgG secretion postinfection; 3 out of 12 mice developed specific antibodies against four HIV-1 antigens
	NOG-Tg(IL-4)	Peripheral blood mononuclear cell	HER2 peptide	Production of anti-HER2 IgG
Preventive vaccine	NSG	FL CD34⁺	Dengue virus serotype-2 (DENV2)	5 out of 27 mice developed DENV2-specific IgM
	NRGF-Tg(HLA-A2)	CB CD34⁺	Yellow fever virus 17D (YFV-17D)	Upon YFV-17D infection, flt3-ligand supplemented mice produced YFV-specific IgM, IgG, and CD8⁺ T cells
	NRG	CB CD34⁺	An adenoviral vector expressing Mycobacterium tuberculosis (MTb) Ag85A	Intranasal vaccination of mice produced MTb antigen-specific CD4⁺ T cells in the airways and protected mice from MTb infection
	DRAG	FL CD34⁺	DNA-encoding Zika prM and E protein	Neutralizing anti-ZIKV E protein IgGs were detected in immunized mice and conferred protection from ZIKV infection
	DRNSG	FL CD34⁺	Plasmodium falciparum circumsporozoite protein (PfCS)	Cytokine-supplemented DRNSG mice produced anti-PfCS IgG and protected mice from rodent malaria
	BLT-BRG	Human fetal liver, thymus, and FL CD34⁺	Zika virus (ZIKV)	Pooled BLT-BRG mice sera demonstrated ZIKV neutralization
	BLTL-NSG	Human fetal liver, thymus, lungs, and FL CD34⁺	Human cytomegalovirus (HCMV)	HCMV-specific IgM detected in 8 of 25 mice

Our Services

Protheragen offers services for the development of humanized animal models targeted for the research and development of therapeutics for ophthalmic diseases. The objective of our services is to help researchers enhance the disease modeling and drug testing processes by providing trustworthy, human-relevant models in order to expedite the development of ophthalmic therapies.

Transgenic Models

Mice/Rabbits: For example, mice with human TCF4 mutations to study FECD or rabbits with human HLA genes for immune response studies.

Zebrafish: Engineered to express human ocular disease genes (e.g., SLC4A11) for high-throughput drug screening.

Xenograft Models

Human Corneal Transplants in Animals: Feline or rabbit models transplanted with human corneal tissues to study rejection and cell-based therapies.

Retinal Cell Grafts: Human retinal pigment epithelium (RPE) cells transplanted into primates to model AMD.

Immune-Humanized Models

Mice with Human Immune Systems: For studying ocular inflammation or graft rejection, such as humanized NOD-scid IL2Rγnull (NSG) mice engrafted with human hematopoietic stem cells.

Customized Humanized Models

Whether you require a model that incorporates specific human cells, tissues, or genetic modifications, our team works closely with you to design and develop a model that aligns perfectly with your research objectives.

Protheragen is dedicated to advancing ophthalmic research by delivering advanced humanized animal models and related services, supporting the development of new therapies for eye diseases. If you are interested in our services, please feel free to contact us.

References

Chen, Jiaxuan, et al. "The development and improvement of immunodeficient mice and humanized immune system mouse models." Frontiers in immunology 13 (2022): 1007579.
Loiseau, Alexis, et al. "Animal models in eye research: focus on corneal pathologies." International Journal of Molecular Sciences 24.23 (2023): 16661.
Ye, Weijian, and Qingfeng Chen. "Potential applications and perspectives of humanized mouse models." Annual Review of Animal Biosciences 10.1 (2022): 395-417.