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2 results on '"Nishad S. Maggirwar"'

1. HIV Persistence, Latency, and Cure Approaches: Where Are We Now?

Author

Tessa C. Chou, Nishad S. Maggirwar, and Matthew D. Marsden

Subjects
HIV, cure, latency, reservoir, persistence, animal model, Microbiology, QR1-502
Abstract

The latent reservoir remains a major roadblock to curing human immunodeficiency virus (HIV) infection. Currently available antiretroviral therapy (ART) can suppress active HIV replication, reduce viral loads to undetectable levels, and halt disease progression. However, antiretroviral drugs are unable to target cells that are latently infected with HIV, which can seed viral rebound if ART is stopped. Consequently, a major focus of the field is to study the latent viral reservoir and develop safe and effective methods to eliminate it. Here, we provide an overview of the major mechanisms governing the establishment and maintenance of HIV latency, the key challenges posed by latent reservoirs, small animal models utilized to study HIV latency, and contemporary cure approaches. We also discuss ongoing efforts to apply these approaches in combination, with the goal of achieving a safe, effective, and scalable cure for HIV that can be extended to the tens of millions of people with HIV worldwide.

Published
2024
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2. Cas9 Ribonucleoprotein Complex Delivery: Methods and Applications for Neuroinflammation

Author

Christopher T. Richie, Brandon K. Harvey, Lee A. Campbell, and Nishad S Maggirwar

Subjects
0301 basic medicine, Computer science, Immunology, Neuroscience (miscellaneous), Mutagenesis (molecular biology technique), Computational biology, Ribonucleoprotein complex, 03 medical and health sciences, 0302 clinical medicine, Genome editing, CRISPR-Associated Protein 9, Immunology and Allergy, CRISPR, Animals, Humans, Neuroinflammation, Ribonucleoprotein, Pharmacology, Gene Editing, Inflammation, Cas9, Gene Transfer Techniques, Extracellular vesicle, 030104 developmental biology, Ribonucleoproteins, CRISPR-Cas Systems, 030217 neurology & neurosurgery
Abstract

The CRISPR/Cas9 system is a revolutionary gene editing technology that combines simplicity of use and efficiency of mutagenesis. As this technology progresses toward human therapies, valid concerns including off-target mutations and immunogenicity must be addressed. One approach to address these issues is to minimize the presence of the CRISPR/Cas9 components by maintaining a tighter temporal control of Cas9 endonuclease and reducing the time period of activity. This has been achieved to some degree by delivering the CRISPR/Cas9 system via pre-formed Cas9 + gRNA ribonucleoprotein (RNP) complexes. In this review, we first discuss the molecular modifications that can be made using CRISPR/Cas9 and provide an overview of current methods for delivering Cas9 RNP complexes both in vitro and in vivo. We conclude with examples of how Cas9 RNP delivery may be used to target neuroinflammatory processes, namely in regard to viral infections of the central nervous system and neurodegenerative diseases. We propose that Cas9 RNP delivery is a viable approach when considering the CRISPR/Cas9 system for both experimentation and the treatment of disease. Graphical Abstract.

Published
2019

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