CRISPR-Based Therapeutic Genome Editing: Strategies and In Vivo Delivery by AAV Vectors

Wang, Dan; Zhang, Feng; Gao, Guangping

doi:10.1016/j.cell.2020.03.023

Cited by 362 publications

(297 citation statements)

References 178 publications

(192 reference statements)

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“…The mice treatments revealed that three forms all functioned well, indicating both viral and non-viral vectors can be used by GIFT. AAV has already become a safe virus vector for the current human gene therapy [58]. However, it is still challenged by high production cost and sometimes immunological rejection.…”

Section: Discussionmentioning

confidence: 99%

Gene interfered-ferroptosis therapy of cancer

Gao

Luo

Lin

et al. 2020

Preprint

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Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we developed a novel therapy named as gene interfered-ferroptosis therapy (GIFT) by combining iron nanoparticles and cancer-specific gene interference. Using a promoter consisted of a NF-κB decoy and a minimal promoter (DMP), we knocked down the expression of two iron metabolism-related genes (FPN and Lcn2) selectively in cancer cells. At the same time, we treated cells with Fe3O4 nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells representing various hematological and solid tumors. However, the same treatment had no effect on normal cells. By using AAV and PEI-coated Fe3O4 nanoparticles as gene vectors, we found that the tumor growth in mice could be also significantly inhibited by the intravenously injected GIFT reagents. By detecting ROS, iron content and gene expression, we confirmed that the mechanism underlying the therapy is gene inference-enhanced ferroptosis.

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Section: Discussionmentioning

confidence: 99%

Gene interfered-ferroptosis therapy of cancer

Gao

Luo

Lin

et al. 2020

Preprint

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“…Importantly, base editing employs cellular mismatch repair machinery and can be applied to reverse these defects in both dividing and terminally differentiated cells. DNA base-editing may prove to be particularly well adapted for correction of mutations within large genes (>4 kb) where vector-mediated delivery is restricted by the cargo limits of AAV vectors 5 . For instance, mutations in the ABCA4 (coding sequence ~6.8 kb) and USH2A (~15.6 kb) genes together account for almost 25% of all inherited retinal diseases 23 .…”

Section: Dna Base Editing and Prime Editingmentioning

confidence: 99%

“…The retina provides a unique opportunity for developing genetic therapies due to its distinct immunological tolerance and unique visual and surgical access, which allows noninvasive assessment of treatment safety and efficacy 4 . Adeno-associated viral (AAV) vectors are the most frequently used vehicles for delivering genetic material into cells due to their high tropism for outer retinal cells and good safety profile 5 . In addition to Luxturna, AAV-mediated gene supplementation therapies to deliver working copies of disease-associated genes into retinal cells in recessive retinal degenerations, for instance, choroideremia and RPGR-associated X-linked retinitis pigmentosa, are being evaluated in advanced stage clinical trials with promising safety and efficacy data 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Genome-Editing Strategies for Treating Human Retinal Degenerations

et al. 2021

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Inherited retinal degenerations (IRDs) are a leading cause of blindness. Although gene-supplementation therapies have been developed, they are only available for a small proportion of recessive IRD mutations. In contrast, genome editing using clustered-regularly interspaced short palindromic repeats (CRISPR) CRISPR-associated (Cas) systems could provide alternative therapeutic avenues for treating a wide range of genetic retinal diseases through targeted knockdown or correction of mutant alleles. Progress in this rapidly evolving field has been highlighted by recent Food and Drug Administration clinical trial approval for EDIT-101 (Editas Medicine, Inc., Cambridge, MA), which has demonstrated efficacious genome editing in a mouse model of CEP290 -associated Leber congenital amaurosis and safety in nonhuman primates. Nonetheless, there remains a significant number of challenges to developing clinically viable retinal genome-editing therapies. In particular, IRD-causing mutations occur in more than 200 known genes, with considerable heterogeneity in mutation type and position within each gene. Additionally, there are remaining safety concerns over long-term expression of Cas9 in vivo . This review highlights (i) the technological advances in gene-editing technology, (ii) major safety concerns associated with retinal genome editing, and (iii) potential strategies for overcoming these challenges to develop clinical therapies.

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“…The NHEJ mechanism of DNA repair is typically ≥ 70% accurate; however, through the processing of the damaged DNA using endonuclease activity, the NHEJ pathway can introduce a small insertion or deletion (indel) at the break site [ 10 ]. The presence of indels can disrupt gene function by causing a frameshift or exon skipping mutation [ 11 ]. In addition, the NHEJ repair pathway can be used to insert exogenous DNA sequences into the break site for targeted gene editing.…”

Section: Fundamentals Of Gene Editingmentioning

confidence: 99%

Delivery Approaches for Therapeutic Genome Editing and Challenges

Ates

Rathbone

Stuart

et al. 2020

Genes

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Impressive therapeutic advances have been possible through the advent of zinc-finger nucleases and transcription activator-like effector nucleases. However, discovery of the more efficient and highly tailorable clustered regularly interspaced short palindromic repeats (CRISPR) and associated proteins (Cas9) has provided unprecedented gene-editing capabilities for treatment of various inherited and acquired diseases. Despite recent clinical trials, a major barrier for therapeutic gene editing is the absence of safe and effective methods for local and systemic delivery of gene-editing reagents. In this review, we elaborate on the challenges and provide practical considerations for improving gene editing. Specifically, we highlight issues associated with delivery of gene-editing tools into clinically relevant cells.

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CRISPR-Based Therapeutic Genome Editing: Strategies and In Vivo Delivery by AAV Vectors

Cited by 362 publications

References 178 publications

Gene interfered-ferroptosis therapy of cancer

Gene interfered-ferroptosis therapy of cancer

Genome-Editing Strategies for Treating Human Retinal Degenerations

Delivery Approaches for Therapeutic Genome Editing and Challenges

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