Review Article |
Featured
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Comment |
From Mendel to a Mendelian disorder: towards a cure for sickle cell disease
To mark the bicentenary of Gregor Mendel’s birth, the authors reflect on progress in the application of genetics and genomics to delivering a cure for sickle cell disease, a classic Mendelian disorder.
- Julie Makani
- , Siana Nkya
- & Lucio Luzzatto
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Research Highlight |
In vivo RNA base editing with circular RNAs
Two recent studies published in Nature Biotechnology describe the engineering of circularized guide RNAs, which allow for programmable RNA base editing in vivo, with vastly improved editing efficiency and durability.
- Michael Attwaters
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In Brief |
Towards gene therapy for Tay-Sachs disease
Flotte et al. describe the first test of adeno-associated virus-based gene therapy for Tay-Sachs disease in humans. Delivery to the thalamus and cerebrospinal fluid was found to be broadly safe, providing a firm basis for future clinical trials.
- Dorothy Clyde
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In Brief |
Fighting fibrosis with transient CAR T cells
A report in Science describes a method to generate transient chimeric antigen receptor (CAR) T cells in vivo via lipid nanoparticle-mediated T cell-targeted delivery of a CAR-encoding nucleoside-modified mRNA.
- Dorothy Clyde
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Review Article |
The potential of mitochondrial genome engineering
The authors review the field of mammalian mitochondrial genome engineering, culminating in the recent development of mitochondrially targeted programmable nucleases and base editors. They describe research that led to the development of animal models of mitochondrial disease, as well as the potential for translating these approaches to the clinic.
- Pedro Silva-Pinheiro
- & Michal Minczuk
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Review Article |
Gene therapy using haematopoietic stem and progenitor cells
Haematopoietic stem and progenitor cell (HSPC) gene therapy using lentiviral or gammaretroviral vectors has now been approved for clinical use. In this Review, Ferrari, Thrasher and Aiuti discuss the history of HSPC gene therapy, the clinical promise of gene-editing HPSCs and the use of HSPC gene therapy to treat specific diseases.
- Giuliana Ferrari
- , Adrian J. Thrasher
- & Alessandro Aiuti
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Review Article |
Engineering adeno-associated virus vectors for gene therapy
Adeno-associated virus (AAV) vector-mediated gene delivery has had long-term therapeutic effects for several diseases, including haemophilia and Duchenne muscular dystrophy. Genetically modifying AAV vectors to increase their transduction efficiency, vector tropism and ability to avoid the host immune response may further increase the success of AAV gene therapy.
- Chengwen Li
- & R. Jude Samulski
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Research Highlight |
Gold rush to gene-editing in the brain
A study in Nature Biomedical Engineering reports improvements in neurological symptoms in a mouse model of fragile X syndrome after non-viral delivery of Cas9 ribonucleoproteins to the brain.
- Michelle Trenkmann
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Research Highlight |
CRISPR therapies — making the grade not the cut
A new study uses CRISPR-based transcriptional modulation as an in vivo therapeutic in various mouse models of human diseases.
- Darren J. Burgess
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Review Article |
Defining and improving the genome-wide specificities of CRISPR–Cas9 nucleases
Applying CRISPR–Cas9 genome editing technologies in safe and reliable ways requires a firm appreciation of the specificity of target-site recognition and cleavage. In this Review the authors discuss various approaches for characterizing off-target effects of CRISPR–Cas9 genome editing, how mechanistic knowledge can drive the engineering of more-specific nucleases, and the implications for research and therapeutic applications.
- Shengdar Q. Tsai
- & J. Keith Joung
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Review Article |
Non-viral vectors for gene-based therapy
This Review introduces the biological barriers to gene deliveryin vivoand discusses recent advances in material sciences, nanotechnology and nucleic acid chemistry that have yielded promising non-viral systems for the delivery of DNA, mRNA, small interfering RNAs and microRNAs, some of which are currently undergoing testing in clinical trials.
- Hao Yin
- , Rosemary L. Kanasty
- & Daniel G. Anderson
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Progress |
Engineering adeno-associated viruses for clinical gene therapy
Although gene delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective for numerous clinical gene therapy applications, many challenges remain. Recent advances in AAV vector development through rational design and directed evolution, as well as in the design of novel genetic cargoes, promise to extend clinical successes of AAV-mediated gene therapy.
- Melissa A. Kotterman
- & David V. Schaffer
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Progress |
Therapy for Duchenne muscular dystrophy: renewed optimism from genetic approaches
Several promising genetic approaches are being investigated for the treatment of Duchenne muscular dystrophy, including traditional gene therapy, stop codon read-through, exon skipping and increased expression of a compensatory gene. The lessons learned should also be valuable for other disorders.
- Rebecca J. Fairclough
- , Matthew J. Wood
- & Kay E. Davies
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From The Editors |
From the editors
Read about prospects for gene-based therapies in our Focus issue this month.
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Review Article |
Current prospects for RNA interference-based therapies
RNA interference can elicit specific gene silencing and so holds great potential for treating infectious or genetic diseases. Several small-RNA-based therapies have now reached clinical trials, but further work is still needed to improve delivery and efficacy.
- Beverly L. Davidson
- & Paul B. McCray Jr
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Review Article |
Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges
Recent clinical and preclinical studies have described exciting results using recombinant adeno-associated virus (AAV) vectors for therapeutic gene transfer in genetic disease. This Review explores the potential for using this form of therapy in the context of different tissues and diseases.
- Federico Mingozzi
- & Katherine A. High
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Review Article |
State-of-the-art gene-based therapies: the road ahead
This Review describes the state-of-the-art accomplishments that have been made with gene-based therapies and the major barriers that need to be overcome before these tools are more widely implemented by the medical community.
- Mark A. Kay
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Review Article |
Ex vivo gene transfer and correction for cell-based therapies
Cell-based therapy is a growing field that exploits advances in stem cell manipulation and gene transfer technologies. This Review discusses the latest developments and crucial challenges for this field, with an emphasis on haematopoietic stem cell gene therapy.
- Luigi Naldini
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Review Article |
Photoreceptor degeneration: genetic and mechanistic dissection of a complex trait
Retinal degeneration due to photoreceptor cell death is a major cause of visual impairment in adults. Over one hundred genes have been implicated, so how does this genetic heterogeneity converge on a shared phenotype? The emerging insights have implications for therapy.
- Alan F. Wright
- , Christina F. Chakarova
- & Shomi S. Bhattacharya
Deafness: from genetic architecture to gene therapy
Human genome editing in heart disease
In vivo gene editing in non-dividing cells
Allele-specific genome editing of disease loci
In vivo selection of gene-corrected cells
Insulating from genotoxicity
Mitochondrial replacement techniques under the spotlight
Correcting genetic defects with CRISPR–Cas9
Re-evaluating gut insulin instinct
Keeping ZFNs on target
Getting RNAi therapies to the brain
MicroRNAs provide powerful postponement