Engineered zinc‐finger nuclease to generate site‐directed modification in the KLF1 gene for fetal hemoglobin induction

Shariati, Laleh; Modarressi, Mohammad Hossein; Tabatabaiefar, Mohammad Amin; Kouhpayeh, Shirin; Hejazi, Zahra; Shahbazi, Mansoureh; Sabzehei, Faezeh; Salehi, Mansoor; Khanahmad, Hossein

doi:10.1002/jcb.28130

Cited by 7 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is the purported mechanism of severe lung injury in COVID-19 patients [ 51 ]. The ability of TRPM2 to respond to oxidative stress made it a promising target for repurposing TRPM2 inhibitor drugs such as fluenamic acid or mefenamic acid, melatonin, and selenium, or for developing new small molecules and therapeutic approaches, such as aptamers [ 52 ] and gene editing tools [ 53 , 54 ].…”

Section: Pathogenesis and Therapeutic Targetsmentioning

confidence: 99%

“…The aforementioned events account for the acute respiratory distress syndrome (ARDS) identified in COVID-10 patients [ 64 , 65 , 66 ]. Activation of TRPM2 increases NLR family pyrin domain containing 3 (NLRP3) activity and IL8 secretion, intensifying inflammation and cytokine storm [ 54 ]. In the inflamed lung tissue, IL8 has a chemotactic role in attracting neutrophils to the lung parenchyma to further exert various pathologic effects.…”

Section: Pathogenesis and Therapeutic Targetsmentioning

confidence: 99%

See 1 more Smart Citation

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

Kouhpayeh

Shariati

Boshtam

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

In late 2019, a new member of the Coronaviridae family, officially designated as “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.

show abstract

Section: Pathogenesis and Therapeutic Targetsmentioning

confidence: 99%

Section: Pathogenesis and Therapeutic Targetsmentioning

confidence: 99%

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

Kouhpayeh

Shariati

Boshtam

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…They demonstrated 7–12% efficiency of homologous recombination [ 99 ], while the iSCeI meganuclease was successfully utilised in gene repair in other reports [ 39 , 100 ]. Other groups showed pre-clinical efficiency of ZFNs in relevant disease models, such as adenosine deaminase deficiency [ 101 ], X-SCID [ 102 , 103 ], and β-thalassemia [ 104 ] or meganucleases for Duchenne muscular dystrophy [ 105 ].…”

Section: Old and Current Applications Of Nilvsmentioning

confidence: 99%

The Old and the New: Prospects for Non-Integrating Lentiviral Vector Technology

Apolonia

2020

Viruses

View full text Add to dashboard Cite

Lentiviral vectors have been developed and used in multiple gene and cell therapy applications. One of their main advantages over other vectors is the ability to integrate the genetic material into the genome of the host. However, this can also be a disadvantage as it may lead to insertional mutagenesis. To address this, non-integrating lentiviral vectors (NILVs) were developed. To generate NILVs, it is possible to introduce mutations in the viral enzyme integrase and/or mutations on the viral DNA recognised by integrase (the attachment sites). NILVs are able to stably express transgenes from episomal DNA in non-dividing cells or transiently if the target cells divide. It has been shown that these vectors are able to transduce multiple cell types and tissues. These characteristics make NILVs ideal vectors to use in vaccination and immunotherapies, among other applications. They also open future prospects for NILVs as tools for the delivery of CRISPR/Cas9 components, a recent revolutionary technology now widely used for gene editing and repair.

show abstract

“…This might be the possible explanation of severe lung injury in COVID -19 patients. Moreover, TRPM2 ability to response to oxidative stress made it a promising target for development of new small molecule and therapeutic approach suchas aptamer(31) and gene editing tools(32,33)(Fig 1).…”

mentioning

confidence: 99%

The Molecular Story of COVID-19; NAD+ Depletion Addresses All Questions in this Infection

Kouhpayeh¹,

Shariati²,

Boshtam³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The emerging new Coronaviridae member, nCoV 19, outbreak announced a pandemic by WHO with an increased morbidity and mortality rate worldwide. nCoV 19 known as the third highly pathogen coronavirus in the human population after the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), the nCoV 19. The renin-angiotensin (RAS) signaling pathway, oxidative stress and cell death, cytokines storm and endothelial dysfunction are four major pathways involved in the pathogenesis of nCoV 19. Acute respiratory distress syndrome (ARDS) generally develops with a massive oxidative/nitrosative stress following virus entry and RAS activation. The DNA damage subsequent to oxidative burst activates poly-ADP ribose polymerase-1 (PARP-1), viral macrodomain (NSP3) poly (ADP-ribose) glycohydrolase (PARG) and transient receptor potential channel, melastatin 2 (TRPM2) in a sequential manner ultimately leading to apoptosis and necrosis due to NAD and ATP depletion. Regarding the molecular mechanisms involved in nCoV 19 pathogenesis, angiotensin II receptor blockers and/or PARP, PARG and TRPM2 blockers could be engaged as therapeutic candidates for inhibition of RAS and quenching oxidative stress, respectively. In this review, the molecular aspects of nCoV 19 pathogenesis would be studied precisely and possible therapeutic targets would be proposed. It is recommended to evaluate the proposed drugs and supplements via registered clinical trials along with conventional guideline-based multi-drug regimen.

show abstract

Engineered zinc‐finger nuclease to generate site‐directed modification in the KLF1 gene for fetal hemoglobin induction

Cited by 7 publications

References 38 publications

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

The Old and the New: Prospects for Non-Integrating Lentiviral Vector Technology

The Molecular Story of COVID-19; NAD<sup>+</sup><sup> </sup>Depletion Addresses All Questions in this Infection

Contact Info

Product

Resources

About