Emerging Landscape of Cell-Penetrating Peptide-Mediated Organelle Restoration and Replacement

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Osteogenesis imperfecta (OI) is an uncommon genetic disorder characterized by shortness of stature, hearing loss, poor bone mass, recurrent fractures, and skeletal abnormalities. Pathogenic variations have been found in over 20 distinct genes that are involved in the pathophysiology of OI, contributing to the disorder's clinical and genetic variability. Although medications, surgical procedures, and other interventions can partially alleviate certain symptoms, there is still no known cure for OI. In this Review, we provide a comprehensive overview of genetic pathogenesis, existing treatment modalities, and new developments in biotechnologies such as gene editing, stem cell reprogramming, functional differentiation, and transplantation for potential future OI therapy.

Section: Acs Pharmacology and Translational Sciencementioning

confidence: 99%

Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches

Sun,

Li,

Wang

et al. 2024

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“…Several intracellular targets involved in different stages of the viral life cycle have been identified as potential targets for nanobodies to inhibit SARS-CoV-2 replication and packaging, such as Mpro, RdRp, and viral N protein. , Although nanobodies’ small size enables us to effectively target intracellular proteins and other targets involved in various cellular pathways, delivering nanobodies into the cytoplasm of target cells is a significant challenge due to the presence of cellular membranes that prevent their entry. There are several approaches to deliver nanobodies into the cytoplasm, including chemical conjugation, cell-penetrating peptides, − and nanoparticle-based delivery systems. , These methods have been used successfully for the delivery of other therapeutic molecules. Thus, the development of nanobodies targeting intracellular targets involved in SARS-CoV-2 replication still holds promise for the development of new therapeutics to combat COVID-19.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

Emerging Landscape of Nanobodies and Their Neutralizing Applications against SARS-CoV-2 Virus

Feng

Wang

2023

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The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has significantly altered people's way of life. Despite widespread knowledge of vaccination, mask use, and avoidance of close contact, COVID-19 is still spreading around the world. Numerous research teams are examining the SARS-CoV-2 infection process to discover strategies to identify, prevent, and treat COVID-19 to limit the spread of this chronic coronavirus illness and restore lives to normalcy. Nanobodies have advantages over polyclonal and monoclonal antibodies (Ab) and Ab fragments, including reduced size, high stability, simplicity in manufacture, compatibility with genetic engineering methods, and lack of solubility and aggregation issues. Recent studies have shown that nanobodies that target the SARS-CoV-2 receptor-binding domain and disrupt ACE2 interactions are helpful in the prevention and treatment of SARS-CoV-2-infected animal models, despite the lack of evidence in human patients. The creation and evaluation of nanobodies, as well as their diagnostic and therapeutic applications against COVID-19, are discussed in this paper.

“…It was first reported in Wuhan, China, in December 2019 and has since become a global pandemic. 1 There have been 768,983,095 confirmed cases of COVID-19 and 6,953,743 deaths worldwide as of August 2023 according to the World Health Organization (WHO). 2 The virus belongs to the family of coronaviruses and shares 79% genome sequence identity with severe acute respiratory syndrome coronavirus (SARS-CoV) and 50% with Middle East respiratory syndrome virus (MERS-CoV), which are two other viruses in the same virus family.…”

mentioning

confidence: 99%

Emerging Landscape of Preclinical Models for Studying COVID-19 Neurologic Diseases

Li,

Wang,

Wang

2023

Self Cite

COVID-19 (Coronavirus Disease 2019) is an infectious disease caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and has globally infected 768 million people and caused over 6 million deaths. COVID-19 primarily affects the respiratory system but increasing reports of neurologic symptoms associated with COVID-19 have been reported in the literature. The exact mechanism behind COVID-19 neurologic pathophysiology remains poorly understood due to difficulty quantifying clinical neurologic symptoms in humans and correlating them to findings in human post-mortem samples and animal models. Thus, robust preclinical experimental models for COVID-19 neurologic manifestations are urgently needed. Here, we review recent advances in in vitro, in vivo, and other models and technologies for studying COVID-19 including primary cell cultures, pluripotent stem cell-derived neurons and organoids, rodents, nonhuman primates, 3D bioprinting, artificial intelligence, and multiomics. We specifically focus our discussion on the contribution, recent advancements, and limitations these preclinical models have on furthering our understanding of COVID-19's neuropathic physiology. We also discuss these models' roles in the screening and development of therapeutics, vaccines, antiviral drugs, and herbal medicine, and on future opportunities for COVID-19 neurologic research and clinical management.