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CRISPER Gene Therapy Recent Trends and Clinical Applications
Published in Yashwant Pathak, Gene Delivery, 2022
Prachi Pandey, Jayvadan Patel, Samarth Kumar
As CRISPR–Cas system is found in bacteria, it undertakes evolution rapidly and eventually may produce new Cas genes which will encode new proteins. Thus, these proteins may have the budding potential for genome editing or other similar applications within the near future. Of late, Cas12a has been known to have great purpose in genome editing. CRISPR technology has also been of great use to treat cancer and other diseases. CRISPR–Cas9 technology experiments are normally performed in vitro in model organisms and stem cells like human pluripotent stem cells (hPSCs). Gene editing by this technology is also conducted in human embryonic stem cells (ESCs) in vitro to correct mutations, but research in ESCs gives rise to many ethical issues. However, it is undeniable that the genome editing of ESCs has the potential to give rise to organisms possessing outstanding desirable qualities. Safety measures are essential while using this technology to prevent its misuse or minimize the risk of the negative impact of genome editing.
Approaches for Identification and Validation of Antimicrobial Compounds of Plant Origin: A Long Way from the Field to the Market
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Lívia Maria Batista Vilela, Carlos André dos Santos-Silva, Ricardo Salas Roldan-Filho, Pollyanna Michelle da Silva, Marx de Oliveira Lima, José Rafael da Silva Araújo, Wilson Dias de Oliveira, Suyane de Deus e Melo, Madson Allan de Luna Aragão, Thiago Henrique Napoleão, Patrícia Maria Guedes Paiva, Ana Christina Brasileiro-Vidal, Ana Maria Benko-Iseppon
The main preclinical toxicological tests that are requested internationally are based on the international guides of the International Council for Harmonization (ICH) number M3 (R2) from the Food and Drug Administration (FDA 2013) and of the European Medicine Agency (EMA 2013). Tests are conducted in vitro using cell culture or in vivo involving rodents and other mammals (Fig. 10.2). In general, preclinical trials assess the toxicity in different model organisms at diverse levels. Acute toxicity in a single dose or repeated doses and reproductive toxicity generally assess how the compound acts in various organ systems in mice, including reproductive organs (in vivo). Genotoxicity and carcinogenicity tests assess the compound’s ability to induce DNA damage and develop a tumor, respectively. Local toxicology observes whether the drug induces an undesirable reaction in the contact region. Pharmacodynamics is an observation of the effects of the compound on organ systems, emphasizing the central nervous, cardiovascular and respiratory systems. Finally, toxicokinetic observes the pathway of the compound throughout the body, including absorption, metabolism and excretion. So far, genotoxicity and toxicokinetic tests can be conducted in vitro (Sjöberg and Jones 2013; Denny and Sterwart 2017; Madia et al. 2021).
Branching out: Specialties and subspecialties in medical genetics
Published in Peter S. Harper, The Evolution of Medical Genetics, 2019
Many of the molecular defects in human malformations proved to be the counterparts of those already recognised in other organisms, not just mammals but distantly related, though well-studied organisms such as Drosophila, yeast and bacteria. This widened the concept of ‘model organisms’ still further, and strengthened the scientific basis of clinical dysmorphology to the extent that human and especially medical data are now often the ‘model’ on which research in other species can be based. The field has now matured to the extent that individual disorders can be attributed to defects in specific developmental pathways, giving a network of ‘inborn errors of development’ akin to the ‘inborn errors of metabolism’ foreseen by Garrod at the beginning of the twentieth century. In the same way that inherited metabolic disease was accompanied by a landmark handbook, The Inherited Basis of Metabolic Disease (Stanbury et al. 1960), so the molecular basis of congenital malformations now has its own comparable volume, Charles Epstein and colleagues’ Inborn Errors of Development, first published in 2004.
Characterization and neuroprotective properties of alkaloid extract of Vernonia amygdalina Delile in experimental models of Alzheimer’s disease
Published in Drug and Chemical Toxicology, 2022
Ganiyu Oboh, Bukola Christiana Adedayo, Mayowa Blessing Adetola, Idowu Sunday Oyeleye, Opeyemi Babatunde Ogunsuyi
An example of a medication that could induce neurodegeneration is scopolamine, known to induce learning and memory deficit in animal subjects (Fadda et al. 2000, Araujo et al. 2005, Hasselmo 2006, Akinyemi et al. 2017). Its mechanism is connected to oxidative damage to neuronal cells relevant to cognitive and memory (Hong et al. 2011a, Pachauri et al. 2015, Ogunsuyi et al. 2018). The vertebrate model organism of human diseases, including AD, is frequently impeded by ethical requirements, time, and cost of taking care of. The utilization of alternative models, such as fruit fly (Drosophila melanogaster [D. melanogaster]) takes into consideration increasingly refined experimental approaches, however, lack of some AD’s pathophysiological features is inevitable (Katja et al. 2013). Notwithstanding, the transgenic species, express human BACE-1, and the amyloid precursor protein (hAPP) (Ogunsuyi et al. 2020).
The CRISPR revolution and its potential impact on global health security
Published in Pathogens and Global Health, 2021
Kyle E. Watters, Jesse Kirkpatrick, Megan J. Palmer, Gregory D. Koblentz
One of the biggest changes in biomedical research brought about by genome editing, and especially CRISPR, is the ability to create new cell and animal models quickly and efficiently. Unlike ZFN and TALEN technologies, CRISPR does not require redesign of the effector nuclease, only the guide RNA, which is much simpler. Synthesizing guides is relatively inexpensive, and many can be tested in a short period of time. Further, the high activity of Cas nucleases results in a higher probability of making a desired mutation or change, which shortens screening times and becomes more significant as the maturation time of the model organism increases [68,69]. The faster turnaround time of new model organisms benefits biological research as a whole, allowing for more appropriate testing environments and less time spent building research materials and more time collecting new data. This was demonstrated during the COVID-19 pandemic with the creation of a mouse model expressing the human angiotensin-converting enzyme 2 (hACE2) using CRISPR-Cas9 in place of the mouse version of the enzyme [70]. The development of monoclonal antibodies (mAbs) and vaccines for prophylactic treatments can also benefit from CRISPR/Cas9 through increased rates of cell line generation as well as the ability to perform genomic screens to identify what epitopes are targeted by mAbs [71].
Exploring neuropeptide signalling through proteomics and peptidomics
Published in Expert Review of Proteomics, 2019
Samantha Louise Edwards, Lucas Mergan, Bhavesh Parmar, Bram Cockx, Wouter De Haes, Liesbet Temmerman, Liliane Schoofs
In peptidomics, in contrast to proteomics, there is no involvement of digestive steps using proteases. Here the peptides are the focus of the analysis, where they are studied as the endogenous, complete sequences. Early pioneering studies in peptidomics relied on Edman degradation for identification [62–64], while modern techniques are based on high throughput MS approaches. These earlier studies mostly focused on peptide content of specific tissues, required huge samples [65], and because of protein degradation (which interferes with the detection of endogenous peptides), these techniques were most productive when applied to dissected tissues rich in peptide content or directly on isolated peptide-containing vesicles, like the DCV [62]. The peptidomics technology [63,66–68] has reduced the time required for peptide isolation and identification from years to days and allows examining many peptides at the same time. In addition, peptidomics is less prone to interference from protein degradation products due to better and faster isolation techniques, requiring smaller samples [69–71]. As peptidomics relies on specialized search algorithms, the applicability of peptidomics is often limited by whether compatible and specialized peptide databases for the species of interest are available [72–76]. In order to get the most out of the gathered data, access to a high quality and curated peptide mass and sequence database is mandatory. As such, comprehensive peptidomics studies are currently primarily relegated for use in well-studied model organisms.