Featured
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News & Views |
An optimized toolkit for prime editing
Prime editing in vivo is systematically improved with an eye to clinical translation.
- Ryan M. Marks
- , Ori Scott
- & Ronald D. Cohn
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Article
| Open Access
In vivo human T cell engineering with enveloped delivery vehicles
Cell-specific molecular delivery with enveloped delivery vehicles enables genome editing ex vivo and in vivo.
- Jennifer R. Hamilton
- , Evelyn Chen
- & Jennifer A. Doudna
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Article |
Engineered serum markers for non-invasive monitoring of gene expression in the brain
Gene expression in the mouse brain is measured with a simple blood draw.
- Sangsin Lee
- , Shirin Nouraein
- & Jerzy O. Szablowski
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News & Views |
Tracing the fate of AAV vectors in the body
A study of AAV gene therapy in monkeys proposes that integrated vectors may drive long-term transgene expression.
- Nerea Zabaleta
- & Irene Gil-Farina
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Patents |
The global patent landscape of mRNA for diagnosis and therapy
The COVID-19 pandemic brought mRNA vaccines to market in a short period, pointing the entire drug development field in the direction of mRNA treatment.
- Mengru Lyu
- , Jiyuan Chen
- & Yuan Gao
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Article |
A highly efficient transgene knock-in technology in clinically relevant cell types
Transgene knock-ins into housekeeping genes lead to high efficiency of cell selection.
- Alexander G. Allen
- , Samia Q. Khan
- & John A. Zuris
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Research Briefing |
Lipid nanoparticle-enabled gene editing in the lung via inhalation
The ability to create in vivo genomic medicines for tissues other than the liver has been impeded by difficulties in delivery. Using a high-throughput platform, we developed lipid nanoparticles that can effectively deliver mRNA and CRISPR–Cas9 gene editing tools to the lungs through intratracheal administration, expanding the potential clinical uses of gene editing and mRNA-based technologies.
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Brief Communication |
Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing
A high-throughput screen improves lipid nanoparticle delivery of gene editors in the lung.
- Bowen Li
- , Rajith Singh Manan
- & Daniel Anderson
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Article |
Targeted DNA integration in human cells without double-strand breaks using CRISPR-associated transposases
Large DNA sequences are integrated into human cells using RNA-guided CRISPR-associated transposases.
- George D. Lampe
- , Rebeca T. King
- & Samuel H. Sternberg
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Research Briefing |
Spatial tropism profiling of AAV vectors by ultrasensitive sequential FISH in tissue
Ultrasensitive sequential fluorescence in situ hybridization (USeqFISH) enables multiplexed detection of the expression of endogenous and exogenous genes delivered by adeno-associated virus (AAV) vectors in intact tissue. USeqFISH provides a spatial map of AAV tropism with high throughput and resolution.
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Research Briefing |
CLASH enables large-scale parallel knock-in for cell engineering
CLASH is a CRISPR-based platform that enables the parallel knock-in via homology-directed repair of a large pool of transgene variants encoded in adeno-associated virus vectors. CLASH can be applied to the systematic and unbiased selection of favorable features in T cells and, in principle, other cell types.
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Article
| Open Access
Spatial transcriptomics for profiling the tropism of viral vectors in tissues
Dual mapping shows localization patterns of AAV and RNA in intact tissues.
- Min J. Jang
- , Gerard M. Coughlin
- & Viviana Gradinaru
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Article
| Open Access
Systematic discovery of recombinases for efficient integration of large DNA sequences into the human genome
Screening recombinases identifies tools for inserting large sequences into the human genome.
- Matthew G. Durrant
- , Alison Fanton
- & Patrick D. Hsu
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Article
| Open Access
Engineering circular RNA for enhanced protein production
Protein expression from circular RNAs is enhanced several hundred-fold by optimizing vector design.
- Robert Chen
- , Sean K. Wang
- & Howard Y. Chang
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Article |
Fludarabine increases nuclease-free AAV- and CRISPR/Cas9-mediated homologous recombination in mice
Fludarabine-induced DNA damage pathways enhance the in vivo efficiency of homologous recombination-based gene editing.
- Shinnosuke Tsuji
- , Calvin J. Stephens
- & Mark A. Kay
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News & Views |
RNA delivery with a human virus-like particle
RNA cargo is transferred into cultured cells using a fully human delivery system.
- Anna Gutkin
- , Daniel Rosenblum
- & Dan Peer
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Article |
Targeting herpes simplex virus with CRISPR–Cas9 cures herpetic stromal keratitis in mice
CRISPR–Cas9 eliminates herpes simplex virus both in the corneal infection site and in the viral reservoir of the trigeminal ganglia.
- Di Yin
- , Sikai Ling
- & Yujia Cai
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Review Article |
The delivery challenge: fulfilling the promise of therapeutic genome editing
As CRISPR therapies move into clinical testing, David Schaffer and colleagues review a raft of different delivery technologies being road tested to address cargo capacity limitations, maximize potency, minimize off-target effects and avoid immunogenicity.
- Joost van Haasteren
- , Jie Li
- & David V. Schaffer
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Article |
Plant gene editing through de novo induction of meristems
Methods to induce edited somatic plant cells to form meristems circumvent tissue culture and enable genome editing of a wider set of plant species.
- Michael F. Maher
- , Ryan A. Nasti
- & Daniel F. Voytas
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Letter |
Harnessing type I CRISPR–Cas systems for genome engineering in human cells
A type I CRISPR–Cas system, rather than the conventional type II CRISPR systems, is adapted for gene editing by fusing Cascade to the FokI nuclease domain.
- Peter Cameron
- , Mary M. Coons
- & Samuel H. Sternberg
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Article |
A highly soluble Sleeping Beauty transposase improves control of gene insertion
A soluble variant of Sleeping Beauty transposase improves control over genomic integration.
- Irma Querques
- , Andreas Mades
- & Orsolya Barabas
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News & Views |
Jumping at the chance for precise DNA integration
CRISPR–Cas-associated transposases enable targeted integration of new sequences into genomes.
- Jennifer B. Kwon
- & Charles A. Gersbach
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News & Views |
Viruses leave their stamp on single cells
A method for 'stamping' viruses achieves efficient transduction of single target cells in cultured tissues and in the mouse brain.
- Ede A Rancz
- & Andreas T Schaefer
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Article |
Virus stamping for targeted single-cell infection in vitro and in vivo
Viruses are transduced to single cells in tissues, organoids and in the mouse brain using mechanical carriers.
- Rajib Schubert
- , Stuart Trenholm
- & Botond Roska
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News Feature |
The 'anti-hype' vaccine
After years under the radar, RNA vaccines are finally emerging as immunotherapies to combat pandemics and cancer. But as Laura DeFrancesco reports, clinical validation remains elusive.
- Laura DeFrancesco
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Letter |
A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear
Efficient gene transfer to the mouse inner ear is achieved with a synthetic adeno-associated viral vector.
- Lukas D Landegger
- , Bifeng Pan
- & Luk H Vandenberghe
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Article |
Regulating the expression of therapeutic transgenes by controlled intake of dietary essential amino acids
Gene therapy is switched on and off by changes in diet.
- Cédric Chaveroux
- , Alain Bruhat
- & Pierre Fafournoux
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Letter |
Targeted gene addition in human CD34+ hematopoietic cells for correction of X-linked chronic granulomatous disease
Targeted genetic correction of hematopoietic stem cells is applied to X-linked chronic granulomatous disease.
- Suk See De Ravin
- , Andreas Reik
- & Harry L Malech
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Letter |
Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain
AAV vectors that efficiently transduce the mouse brain after intravenous injection are generated with a CRE-dependent selection system.
- Benjamin E Deverman
- , Piers L Pravdo
- & Viviana Gradinaru
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Article |
Genomic discovery of potent chromatin insulators for human gene therapy
A genome-wide analysis of CTCF binding sites yields compact sequence elements that function as chromatin insulators.
- Mingdong Liu
- , Matthew T Maurano
- & George Stamatoyannopoulos
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Letter |
Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases
Delivery of CRISPR-Cas nucleases using bacteriophage enables targeted killing of microbes in a population
- Robert J Citorik
- , Mark Mimee
- & Timothy K Lu
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Letter |
Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing
The genetic complexity of human leukemia is modeled using the CRISPR-Cas9 system in mice.
- Dirk Heckl
- , Monika S Kowalczyk
- & Benjamin L Ebert
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Letter |
Virally mediated optogenetic excitation and inhibition of pain in freely moving nontransgenic mice
Viral delivery of opsins to peripheral nociceptors allows optogenetic stimulation and inhibition of pain in non-transgenic freely moving mice.
- Shrivats Mohan Iyer
- , Kate L Montgomery
- & Scott L Delp
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News & Views |
A window onto siRNA delivery
Two studies trace the intracellular trafficking of siRNA delivered by lipid nanoparticles.
- Yuhua Wang
- & Leaf Huang
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News & Views |
Reprogramming paces the heart
Rodent cardiomyocytes are converted into pacemaker cells by viral delivery of a single transcription-factor gene.
- Edward G Lakatta
- & Victor A Maltsev
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Article |
Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18
Rodent cardiomyocytes are converted to sinoatrial-node pacemaker cells by expression of the transcription factor Tbx18.
- Nidhi Kapoor
- , Wenbin Liang
- & Hee Cheol Cho
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Correspondence |
Addgene provides an open forum for plasmid sharing
- Melanie Herscovitch
- , Eric Perkins
- & Melina Fan
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Correspondence |
Exploiting host molecules to augment mycoinsecticide virulence
- Yanhua Fan
- , Dov Borovsky
- & Nemat O Keyhani
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Resource |
A resource of vectors and ES cells for targeted deletion of microRNAs in mice
Prosser et al. describe a resource of mouse embryonic stem cell clones harboring deletions that target 392 microRNA loci.. Because the targeting cassettes can be readily replaced by reporter genes, conditional alleles and other variants, the lines should facilitate a broad range of studies into microRNA function.
- Haydn M Prosser
- , Hiroko Koike-Yusa
- & Allan Bradley
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News & Views |
SiRNA delivery with exosome nanoparticles
A natural system for ferrying RNA between cells is used to transport siRNA to the mouse brain.
- Jasper G van den Boorn
- , Martin Schlee
- & Gunther Hartmann
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Letter |
Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
Delivery of therapeutic siRNA to specific tissues is a major challenge. Alvarez-Erviti et al. show that exosomes—small vesicles that are naturally secreted by many animal cells—can be engineered to transport siRNA specifically to the brain in mice.
- Lydia Alvarez-Erviti
- , Yiqi Seow
- & Matthew J A Wood
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Feature |
Gene therapy finds its niche
Gene therapy is finally poised to make a contribution to the treatment of debilitating, highly penetrant genetic diseases that have proved intractable to other regimens.
- Cormac Sheridan
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Brief Communication |
A robust system for production of minicircle DNA vectors
Minicircle DNA vectors are superior to plasmids for long-term transgene expression but are not in widespread use because of a laborious production process. Kay et al. present an improved protocol for generating minicircles that makes them a viable alternative to plasmids for gene transfer studies.
- Mark A Kay
- , Cheng-Yi He
- & Zhi-Ying Chen
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News & Views |
A synthetic DNA transplant
The complete set of tools needed to synthesize a functional genome and transplant it into a mycoplasma cell opens up the possibility of mixing and matching natural and synthetic DNA to make genomes with new capabilities.
- Mitsuhiro Itaya
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Letter |
RETRACTED ARTICLE: Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN
Spinal muscular atrophy is an autosomal recessive disease of motor neurons caused by lack of the SMN gene. Foust et al. achieve long-term correction of the disease phenotype in a mouse model by intravenous delivery of SMN using the viral vector scAAV9.
- Kevin D Foust
- , Xueyong Wang
- & Brian K Kaspar
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Letter |
Rational design of cationic lipids for siRNA delivery
Efficient siRNA delivery remains a key challenge to realizing the full potential of RNAi-based therapeutics. Semple et al. accomplish unprecedented potency for liposome-mediated siRNA delivery by applying rational design to refine an empirically identified cationic lipid widely regarded as the benchmark for use in lipid nanoparticles.
- Sean C Semple
- , Akin Akinc
- & Michael J Hope
An oncolytic virus–T cell chimera for cancer immunotherapy
A case of mistaken identity