A toolmaker’s perspective on CRISPR-directed gene editing as a therapeutic strategy for leukemia and beyond

Gene Editing and Modulation: the Holy Grail for the Genetic Epilepsies?

Neurotherapeutics ◽

10.1007/s13311-021-01081-y ◽

2021 ◽

Author(s):

Jenna C. Carpenter ◽

Gabriele Lignani

Keyword(s):

Precision Medicine ◽

Neurological Disorder ◽

Gene Editing ◽

Therapeutic Strategy ◽

Therapeutic Potential ◽

Single Gene ◽

Drug Resistant ◽

Holy Grail ◽

Effective Therapeutic Strategy ◽

Genetic Epilepsies

AbstractEpilepsy is a complex neurological disorder for which there are a large number of monogenic subtypes. Monogenic epilepsies are often severe and disabling, featuring drug-resistant seizures and significant developmental comorbidities. These disorders are potentially amenable to a precision medicine approach, of which genome editing using CRISPR/Cas represents the holy grail. Here we consider mutations in some of the most ‘common’ rare epilepsy genes and discuss the different CRISPR/Cas approaches that could be taken to cure these disorders. We consider scenarios where CRISPR-mediated gene modulation could serve as an effective therapeutic strategy and discuss whether a single gene corrective approach could hold therapeutic potential in the context of homeostatic compensation in the developing, highly dynamic brain. Despite an incomplete understanding of the mechanisms of the genetic epilepsies and current limitations of gene editing tools, CRISPR-mediated approaches have game-changing potential in the treatment of genetic epilepsy over the next decade.

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Optogenetic regulation of embryo implantation in mice using photoactivatable CRISPR-Cas9

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2016850117 ◽

2020 ◽

Vol 117 (46) ◽

pp. 28579-28581

Author(s):

Tomoka Takao ◽

Moritoshi Sato ◽

Tetsuo Maruyama

Keyword(s):

Leukemia Inhibitory Factor ◽

Gene Editing ◽

Therapeutic Strategy ◽

Molecular Mechanisms ◽

Light Emitting Diode ◽

Embryo Implantation ◽

Light Emitting ◽

Spatiotemporal Expression ◽

Fertilized Egg

Embryo implantation is achieved upon successful interaction between a fertilized egg and receptive endometrium and is mediated by spatiotemporal expression of implantation-associated molecules including leukemia inhibitory factor (LIF). Here we demonstrate, in mice, that LIF knockdown via a photoactivatable CRISPR-Cas9 gene editing system and illumination with a light-emitting diode can spatiotemporally disrupt fertility. This system enables dissection of spatiotemporal molecular mechanisms associated with embryo implantation and provides a therapeutic strategy for temporal control of reproductive functions in vivo.

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Towards a novel therapy against AIDS

10.31219/osf.io/3yx7t ◽

2019 ◽

Author(s):

Adrien Locatelli

Keyword(s):

Gene Editing ◽

Therapeutic Strategy ◽

Lentiviral Vector ◽

Experimental Treatment ◽

Novel Therapy ◽

Infected People ◽

The Moment ◽

First Time ◽

Puromycin Resistance Gene

AIDS is an infectious disease that kills over a million people per year. Very recently, Dash et al have for the first time reached the functional cure in HIV-infected humanized mice using CRISPR-Cas9 in combination with LASER ART, and this with a success of one third. Here, I use a theoretical approach to design a therapeutic strategy applicable to humans and different from that of Dash et al. The experimental treatment presented here includes the injection of an Env-directed integrase-defective CRISPR gene-editing lentiviral vector able to express quintuplex gRNAs plus the humanized SpCas9 and the puromycin resistance gene linked by T2A, preceded by a plasma/leukapheresis and the injection of an immunosuppressive cocktail, and followed by an in vivo positive selection. My protocol could have a major impact on HIV-infected people in the event of confirmation by a clinical trial, and it is possible that it becomes a reference treatment against AIDS, although, for the moment, it is only at the stage of hypothesis and theory.

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CRISPR to the Rescue: Advances in Gene Editing for the FMR1 Gene

Brain Sciences ◽

10.3390/brainsci9010017 ◽

2019 ◽

Vol 9 (1) ◽

pp. 17 ◽

Cited By ~ 6

Author(s):

Carolyn Yrigollen ◽

Beverly Davidson

Keyword(s):

Clinical Trials ◽

Fragile X Syndrome ◽

Gene Editing ◽

Therapeutic Strategy ◽

Therapeutic Potential ◽

Fragile X ◽

Genetic Disorders ◽

Treatment Strategies ◽

Gene Pathway ◽

Ataxia Syndrome

Gene-editing using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is promising as a potential therapeutic strategy for many genetic disorders. CRISPR-based therapies are already being assessed in clinical trials, and evaluation of this technology in Fragile X syndrome has been performed by a number of groups. The findings from these studies and the advancement of CRISPR-based technologies are insightful as the field continues towards treatments and cures of Fragile X-Associated Disorders (FXADs). In this review, we summarize reports using CRISPR-editing strategies to target Fragile X syndrome (FXS) molecular dysregulation, and highlight how differences in FXS and Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) might alter treatment strategies for each syndrome. We discuss the various modifications and evolutions of the CRISPR toolkit that expand its therapeutic potential, and other considerations for moving these strategies from bench to bedside. The rapidly growing field of CRISPR therapeutics is providing a myriad of approaches to target a gene, pathway, or transcript for modification. As cures for FXADs have remained elusive, CRISPR opens new avenues to pursue.

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