Humanised mice can provide researchers with insights into infections such as HIV, Coronavirus, Zikavirus and Dengue and thus help in findings ways to eradicate them, said Dr.Santhi Gorantla, Professor, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medica lCenter (UNMC) Omaha.
She was speaking at a plenary session on “Diagnosis And Treatment Of Diseases By Exploiting Genomics, Zebrafish, Humanized Mouse And Holistic Models,” during the 108th Indian Science Congress today.
Humanized mouse is a general term that refers to a mouse that has been engrafted with something from a human. This could be a short strand of human DNA, human tissue, a human tumor, a humanized immune system, or parts of the human microbiome. The latest biomedical breakthroughs are utilizing more and more humanized mice.
Dr. Gorantla said, studies on the pathogenesis of emerging viruses that present a global threat are critical for pathogen classification and therapeutic and vaccine development. Humanized mice contribute to formerly inaccessible insight into human-specific infections in a host-specific manner as observed in patients.
Humanized mice are used for the studies of Human Immunodeficiency Virus (HIV-1), Zika virus (ZIKV), Coronavirus 2 (SARS-CoV-2), and Dengue virus (DENV) infections. “We recently developed new and advanced humanized mice dually reconstituted with human immune system and glial cells to study viral infection in central nervous system (CNS). Recently, we also demonstrated for the first time in a humanized mouse model that HIV can be eradicated using a CRIPSR/Cas9 gene excision system,” she said.
Currently her team is testing different CRIPSPR/Cas9 delivery methods like lipid nanoparticles for the clinical translation of this HIV eradication strategy. While humanized mice are extensively used for HIV- infection and therapeutic development, they have been employed in several other areas of research, such as, bacterial and viral infections, cancer, regenerative medicine, immune system development and immunotherapeutics.
The session was chaired by Prasad Dhulipala, Project Manager, Celland GeneT herapy, CDMO Miltenyi BiotecGaithersburg, USA. He spoke on Next Generation Sequencing, Array CGH and Whole Genome Amplification for Genetic Diagnostics.
He explained that genetic diseases are hall marks of various diseases such as cancer, mental retardation, birth defects and neurodegenerative diseases. Identifying genomic alterations and the genes they contain will provide molecular targets for diagnosis and therapy.
He said, clinical laboratories have increasingly adopted next generation sequencing (NGS) as a standard for the diagnosis of hereditary disorders. NGS methods can be used to detect either germline or somatic mutations. The validity and utility of NGS-based panel testing has been demonstrated for a wide range of conditions including: hearing loss, vision loss, cardiovascular disorders, renal disorders, neurologic disorders, and cancer predispositions.
Similarly, Comparative Genome Hybridization (CGH) is a technique used in cytogenetic laboratories using chromosome metaphase spreads. Until NGS became available array CGH isone of the most powerful tools in diagnostic clinical pathology. He also elaborated on Whole GenomeAmplification (WGA ) method, RT-PCR and real time RT-PCR.
Prof. Pudur Jagadeeswaran, Department of Biological Sciences, University of North Texas, Denton, USA, gave a lecture on “Genome-wide knockdowns in adult zebrafish and discovery of novel genes in hemostasis and antithrombotic drugs.”
Hemostasis is a defense mechanism to prevent organisms with a circulatory system from bleeding in the event of an injury. Despite the contribution of several laboratories regarding coagulation and anticoagulation, as well as platelet function, these factors are poorly understood, he said.
Given that the human genome has 25,000 genes, it is predicted at least 10% of these genes must play a role related to hemostasis. However, the factors known so far are approximately 200. Thus, there are about 2300 genes that remain to be discovered. Prof. Jagdeeswaran said, it will take decades before accomplishing this goal. Thus, knockdowns of human orthologues in zebrafish will yield quicker information.
“We developed knockdown methods in the adult zebrafishthat have high throughout. In this method, 4000 knockdown hybrid injections could then screen the entire genome,” he said.
Dr. Srujana Naramala, Director, Sparsh Holistic Healing Hub, Bengaluru, spoke on Holistic Healing through Reiki and Psycho-spiritual Practices.
