Clustered regularly interspaced short palindromic repeats, a glimpse – impacts in molecular biology, trends and highlights

Author(s):  
Dhivya Selvaraj ◽  
Rajni Dawar ◽  
Pradeep Kumar Sivakumar ◽  
Anita Devi

Abstract Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a novel molecular tool. In recent days, it has been highlighted a lot, as the Nobel prize was awarded for this sector in 2020, and also for its recent use in Covid-19 related diagnostics. Otherwise, it is an eminent gene-editing technique applied in diverse medical zones of therapeutics in genetic diseases, hematological diseases, infectious diseases, etc., research related to molecular biology, cancer, hereditary diseases, immune and inflammatory diseases, etc., diagnostics related to infectious diseases like viral hemorrhagic fevers, Covid-19, etc. In this review, its discovery, working mechanisms, challenges while handling the technique, recent advancements, applications, alternatives have been discussed. It is a cheaper, faster technique revolutionizing the medicinal field right now. However, their off-target effects and difficulties in delivery into the desired cells make CRISPR, not easily utilizable. We conclude that further robust research in this field may promise many interesting, useful results.

2009 ◽  
Vol 4 (5) ◽  
pp. 289-290
Author(s):  
Masayuki Saijo

Thanks to the improvement of living standard and hygiene as well as to the development of the therapeutics, such as antimicrobial agents, diagnostics, vaccines, the mortality and morbidity rates due to infectious diseases have been dramatically improved in developed countries. However, the mortality and morbidity of infectious diseases, respiratory and gastrointestinal tract infections are still very high and the leading causes of fatalities in developing countries. Furthermore, emerging and reemerging infections frequently occur locally and internationally. For instance, the 2009 influenza virus A/H1N1-associated pandemic has emerged and raised public anxiety levels. It is evident that we live in an environment in which infectious diseases are commonly transmitted. Human activities are closely related to the emergence of newly identified infectious diseases. In this issue, the background of the emergence and reemergence of infectious diseases is reviewed. The infectious diseases that might raise public anxiety, such as Nipah encephalitis, rabies, and influenza are focused on and reviewed. The influenza pandemic and imported infectious diseases, which may cross borders, are also reviewed. Infectious diseases associated with natural disasters are reviewed for the sake of future preparedness. The hemorrhagic fevers, such as Ebola and Marburg hemorrhagic fevers, cause severe infections and have very high mortality rates. The diagnostic systems developed for viral hemorrhagic fevers developed in Japan are introduced. The international situation regarding the development of biosafety level 4 (BSL-4) laboratories is introduced. In the review, it is emphasized that BSL-4 laboratories should be operated in Japan, although viral hemorrhagic fevers are not prevalent in Japan. Furthermore, preparedness strategies for large-scale outbreaks of infectious diseases are presented. I believe these papers will help preparations against the infectious diseases associated with disastrous events. I would be very glad if the readers understood the background of emerging and reemerging infectious diseases and noticed that efficacious preparedness for such infections diseases, preparedness based on the scientific studies and empirical evidence, is urgently required. Finally, I sincerely appreciate the contributions by the authors of and the reviewers for the papers, which appear in this issue of the journal, Journal of Disaster Research.


Author(s):  
Toshiaki Iba ◽  
JH Levy ◽  
Marcel Levi

A number of viral infectious diseases have emerged or reemerged from wildlife vectors that have generated serious threats to global health. Increased international traveling and commerce increase the risk of transmission of viral or other infectious diseases. In addition, recent climate changes accelerate the potential spread of domestic disease. The Coronavirus disease 2019 (COVID-19) pandemic is an important example of the worldwide spread, and the current epidemic will unlikely be the last. Viral hemorrhagic fevers, such as Dengue and Lassa fevers, may also have the potential to spread worldwide with a significant impact on public health with unpredictable timing. Based on the important lessons learned from COVID-19, it would be prudent to prepare for future pandemics of life-threatening viral diseases. Among the various threats, this review focuses on the coagulopathy of acute viral infections since hypercoagulability has been a major challenge in COVID-19, but represents a different presentation compared to viral hemorrhagic fever. However, both thrombosis and hemorrhage are understood as the result of thromboinflammation due to viral infections, and the role of anticoagulation is important to consider.


2009 ◽  
Vol 4 (5) ◽  
pp. 315-321
Author(s):  
Masayuki Saijo ◽  
◽  
Shigeru Morikawa ◽  
Ichiro Kurane

Given the real possibility of hemorrhagic fever viruses such as ebola (EBOV), Marburg (MARV), Crimean-Congo hemorrhagic fever (CCHFV), and Lassa (LASV) viruses being introduced into virus-free nations such as Japan, the need arises for concomitant diagnostics even where such diseases are not endemic. Hemorrhagic fever viruses classified as biosafety level-4 (BSL-4) pathogens can only be manipulated in BSL-4 laboratories, making it difficult for nations such as Japan, having no BSL-4 laboratories, to develop required diagnostic assays. To circumvent this problem, diagnostic assays with recombinant viral antigens have been developed at the National Institute of Infectious Diseases, Tokyo, Japan (NIID). Diagnostics such as enzyme immunoassays for detecting viral hemorrhagic antibodies and antigens were developed using recombinant nucleoproteins (rNPs) of EBOV, MARV, CCHFV, and LASV for use as antigens. Immunoglobulin-G (IgG)-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay using rNPs were confirmed to be highly sensitive and specific in detecting these antibodies. Sandwich antigen (Ag) capture ELISA was also developed for detecting these antigens. The sections that follow detail diagnostics developed at the NIID.


Author(s):  
Wenyi Liu ◽  
Luoxi Li ◽  
Jianxin Jiang ◽  
Min Wu ◽  
Ping Lin

Abstract Clustered regularly interspaced short palindromic repeats-CRISPR associated systems (Cas) are efficient tools for targeting specific genes for laboratory research, agricultural engineering, biotechnology, and human disease treatment. Cas9, by far the most extensively used gene-editing nuclease, has shown great promise for the treatment of hereditary diseases, viral infection, cancers and so on. Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications. Despite the fast progress in basic researches and clinical tests, some underlying problems present continuous, significant challenges, such as editing efficiency, relative difficulty in delivery, off-target effects, immunogenicity, etc. This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing tool-kits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development. CRISPR-Cas systems, as a powerful gene-editing approach, will offer great hopes in clinical treatments for many individuals with currently incurable diseases.


Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 701
Author(s):  
Ovidiu Bîcă ◽  
Ioan Sârbu ◽  
Carmen Iulia Ciongradi

This article reviews the latest information about preserving reproductive potential that can offer enhanced prospects for future conception in the pediatric male population with cancer, whose fertility is threatened because of the gonadotoxic effects of chemotherapy and radiation. An estimated 400,000 children and adolescents aged 0–19 years will be diagnosed with cancer each year. Fertility is compromised in one-third of adult male survivors of childhood cancer. We present the latest approaches and techniques for fertility preservation, starting with fertility preservation counselling, a clinical practice guideline used around the world and finishing with recent advances in basic science and translational research. Improving strategies for the maturation of germ cells in vitro combined with new molecular techniques for gene editing could be the next scientific keystone to eradicate genetic diseases such as cancer related mutations in the offspring of cancer survivors.


2021 ◽  
Vol 7 (3) ◽  
pp. eaba1028
Author(s):  
Rachel S. Riley ◽  
Meghana V. Kashyap ◽  
Margaret M. Billingsley ◽  
Brandon White ◽  
Mohamad-Gabriel Alameh ◽  
...  

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)–mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Chenya Zhuo ◽  
Jiabin Zhang ◽  
Jung-Hwan Lee ◽  
Ju Jiao ◽  
Du Cheng ◽  
...  

AbstractThe clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) gene editing technology, as a revolutionary breakthrough in genetic engineering, offers a promising platform to improve the treatment of various genetic and infectious diseases because of its simple design and powerful ability to edit different loci simultaneously. However, failure to conduct precise gene editing in specific tissues or cells within a certain time may result in undesirable consequences, such as serious off-target effects, representing a critical challenge for the clinical translation of the technology. Recently, some emerging strategies using genetic regulation, chemical and physical strategies to regulate the activity of CRISPR/Cas9 have shown promising results in the improvement of spatiotemporal controllability. Herein, in this review, we first summarize the latest progress of these advanced strategies involving cell-specific promoters, small-molecule activation and inhibition, bioresponsive delivery carriers, and optical/thermal/ultrasonic/magnetic activation. Next, we highlight the advantages and disadvantages of various strategies and discuss their obstacles and limitations in clinical translation. Finally, we propose viewpoints on directions that can be explored to further improve the spatiotemporal operability of CRISPR/Cas9.


1998 ◽  
Vol 11 (3-4) ◽  
pp. 391-395 ◽  
Author(s):  
Rivka Carmi ◽  
Khalil Elbedour ◽  
Dahlia Wietzman ◽  
Val Sheffield ◽  
Ilana Shoham-Vardi

The ArgumentThe remarkable progress in modern genetic technology enables the identification of genes causing devastating diseases and thereby the development of tools for prenatal diagnosis and carrier detection. To implement the results of genetic research in traditional societies, where genetic diseases are more prevalent due to inbreeding, necessitates a culturally appropriate approach that also promotes traditional and societal values important to the relevant community. This paper presents our experience with implementing the results of modern genetic research among the traditional community of the Negev Bedouin of Israel. Although the benefit of using those results for the prevention of genetic diseases seems obvious, successful implementation relies on a carefully designed educational program aimed at changing culturally related attitudes and perceptions. Such a program should attend to the needs of the community and be sensitive to its traditional values.


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