Combining Engineered Nucleases with Adeno-associated Viral Vectors for Therapeutic Gene Editing

Epstein, Benjamin E.; Schaffer, David V.

doi:10.1007/978-3-319-63904-8_2

Cited by 13 publications

(11 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The risk of this CRISPR/Cas system inducing off-target effects, such as undesired insertions and deletions of DNA in off-target sequences, will thus be quite high. 6 Although many reports on off-target effects caused by CRISPR/Cas have been published, [11][12][13] there is as yet no standard method. It is, however, difficult to characterize or detect the exact off-target effects that occur rarely, particularly those seen in only a small number of cells.…”

Section: Classification Of Genome-editing Technologies and Challengesmentioning

confidence: 99%

“…Early clinical studies made use of adenovirus, 5 adeno-associated viral vectors, 6 or plasmids 7 to express genome-editing enzymes, and mRNAs 8 coding ZFNs or TALENs were also used. The direct introduction of genome-editing enzymes to modify a target gene have also been explored in both ex vivo and in vivo treatments.…”

Section: Classification Of Genome-editing Products For Gene Therapymentioning

confidence: 99%

“…According to the information on the National Institutes of Health (NIH) ClinicalTrial website, many clinical trials of viral vectors, including adenovirus, AAV and others, have been conducted to introduce ZFN or CRISPR/Cas into a cell for genome-editing gene therapy. 6 , 16 Quality control measures for current gene therapy products can also be applied to gene therapy using viral or plasmid vectors 17 coding a genome-editing enzyme gene. For the past three decades, ∼4,000 clinical protocols for gene therapy have been conducted or are ongoing worldwide (NIH ).…”

Section: Classification Of Genome-editing Technologies and Challengesmentioning

confidence: 99%

See 2 more Smart Citations

Aspects of Gene Therapy Products Using Current Genome-Editing Technology in Japan

Yamaguchi

Uchida²,

Okada

et al. 2020

Human Gene Therapy

View full text Add to dashboard Cite

The development of genome-editing technology could lead to breakthrough gene therapy. Genome editing has made it possible to easily knock out or modify a target gene, while current gene therapy using a virus vector or plasmid hampering modification with respect to gene replacement therapies. Clinical development using these genome-editing tools is progressing rapidly. However, it is also becoming clear that there is a possibility of unintended gene sequence modification or deletion, or the insertion of undesired genes, or the selection of cells with abnormalities in the cancer suppressor gene p53; these unwanted actions are not possible with current gene therapy. The Science Board of the Pharmaceuticals and Medical Devices Agency of Japan has compiled a report on the expected aspects of such genomeediting technology and the risks associated with it. This article summarizes the history of that discussion and compares the key concepts with information provided by other regulatory authorities.

show abstract

Section: Classification Of Genome-editing Technologies and Challengesmentioning

confidence: 99%

Section: Classification Of Genome-editing Products For Gene Therapymentioning

confidence: 99%

Section: Classification Of Genome-editing Technologies and Challengesmentioning

confidence: 99%

See 1 more Smart Citation

Aspects of Gene Therapy Products Using Current Genome-Editing Technology in Japan

Yamaguchi

Uchida²,

Okada

et al. 2020

Human Gene Therapy

View full text Add to dashboard Cite

show abstract

“…Given the great potential of viral vectors in gene and cell therapy, five major classes of viral vectors-retroviruses [38], lentiviruses [39,40], adenoviruses [41,42], AAVs [43,44], and baculoviruses [45,46]-have been used to deliver CRISPR components into mammalian cells for targeted genome editing. The advantages and disadvantages of using these viral vectors for in vivo delivery of the CRISPR transgenes have been extensively reviewed [43,[47][48][49]. In Table 2, we list the general characteristics and applications of various viral delivery vectors.…”

Section: Crispr/cas9 Delivery and Gene Therapymentioning

confidence: 99%

CRISPR-ERA for Switching Off (Onco) Genes

Sánchez-Martı́n¹,

García‐Tuñón²

2019

Modulating Gene Expression - Abridging the RNAi and CRISPR-Cas9 Technologies

View full text Add to dashboard Cite

Genome-editing nucleases like the popular CRISPR/Cas9 enable the generation of knockout cell lines and null zygotes by inducing site-specific double-stranded breaks (DSBs) within a genome. In most cases, when a DNA template is not present, the DSB is repaired by nonhomologous end joining (NHEJ), resulting in small nucleotide insertions or deletions that can be used to construct knockout alleles. However, for several reasons, these mutations do not produce the desired null result in all cases, instead generating a similar protein with functional activity. This undesirable effect could limit the therapeutic efficiency of gene therapy strategies focused on abrogating oncogene expression by CRISPR/ Cas9 and should be taken into account. This chapter reviews the irruption of CRISPR technology for gene silencing and its application in gene therapy.

show abstract

“…Given the great potential of viral vectors in gene and cell therapy, five major classes of viral vectors—retroviruses 19 , lentiviruses 20 , 21 , adenoviruses 22 , 23 , AAVs 24 , 25 , and baculoviruses 26 , 27 —have been employed to deliver CRISPR components into mammalian cells for targeted genome editing. The advantages and disadvantages of using these viral vectors for in vivo delivery of the CRISPR transgenes have been extensively reviewed 24 , 28 – 30 . In Table 1 , we listed general characteristics and applications of various viral delivery vectors.…”

Section: Introductionmentioning

confidence: 99%

In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease

2017

View full text Add to dashboard Cite

Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics.

show abstract

Combining Engineered Nucleases with Adeno-associated Viral Vectors for Therapeutic Gene Editing

Cited by 13 publications

References 69 publications

Aspects of Gene Therapy Products Using Current Genome-Editing Technology in Japan

Aspects of Gene Therapy Products Using Current Genome-Editing Technology in Japan

CRISPR-ERA for Switching Off (Onco) Genes

In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease

Contact Info

Product

Resources

About