Gene therapy

  • Article
    | Open Access

    Replacing mutant genes with wildtype copies using adeno-associated virus (AAV) has been explored for the treatment of inherited retinopathies, but the low cargo limit restricts its use. Here the authors describe a single AAV platform that allows local replacement of a mutated sequence with its wildtype counterpart, based on combined CRISPR-Cas9 and micro-homology-mediated end joining.

    • Koji M. Nishiguchi
    • , Kosuke Fujita
    • , Fuyuki Miya
    • , Shota Katayama
    •  & Toru Nakazawa
  • Article
    | Open Access

    Vectors used in gene therapy for hemoglobin disorders carry globin in a reverse-orientation to prevent the loss of key regulatory elements by RNA splicing, but this limits their efficiency. Here, the authors develop a vector carrying β-globin in a forward orientation and show that it has improved titers and transduction efficiency in humanized mice and nonhuman primates.

    • Naoya Uchida
    • , Matthew M. Hsieh
    • , Lydia Raines
    • , Juan J. Haro-Mora
    • , Selami Demirci
    • , Aylin C. Bonifacino
    • , Allen E. Krouse
    • , Mark E. Metzger
    • , Robert E. Donahue
    •  & John F. Tisdale
  • Article
    | Open Access

    In-depth characterization of adeno-associated virus (AAV)-mediated CRISPR delivery is still lacking. Here, the authors show high levels of integration into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in vivo.

    • Killian S. Hanlon
    • , Benjamin P. Kleinstiver
    • , Sara P. Garcia
    • , Mikołaj P. Zaborowski
    • , Adrienn Volak
    • , Stefan E. Spirig
    • , Alissa Muller
    • , Alexander A. Sousa
    • , Shengdar Q. Tsai
    • , Niclas E. Bengtsson
    • , Camilla Lööv
    • , Martin Ingelsson
    • , Jeffrey S. Chamberlain
    • , David P. Corey
    • , Martin J. Aryee
    • , J. Keith Joung
    • , Xandra O. Breakefield
    • , Casey A. Maguire
    •  & Bence György
  • Article
    | Open Access

    CRISPR-Cas9 genome editing is presumed to knock out gene function by generating a frameshift during NHEJ repair. Here, the authors investigate mRNA and protein expression in edited lines and find genome editing can generate internal ribosome entry sites or alternatively spliced variants.

    • Rubina Tuladhar
    • , Yunku Yeu
    • , John Tyler Piazza
    • , Zhen Tan
    • , Jean Rene Clemenceau
    • , Xiaofeng Wu
    • , Quinn Barrett
    • , Jeremiah Herbert
    • , David H. Mathews
    • , James Kim
    • , Tae Hyun Hwang
    •  & Lawrence Lum
  • Article
    | Open Access

    Mucopolysaccharidosis type I (MPSI) is a lysosomal storage disease caused by insufficient iduronidase (IDUA) activity. Here, the authors use an ex vivo genome editing approach to overexpress IDUA in human hematopoietic stem and progenitor cells and show it can phenotypically correct MSPI in mouse model.

    • Natalia Gomez-Ospina
    • , Samantha G. Scharenberg
    • , Nathalie Mostrel
    • , Rasmus O. Bak
    • , Sruthi Mantri
    • , Rolen M. Quadros
    • , Channabasavaiah B. Gurumurthy
    • , Ciaran Lee
    • , Gang Bao
    • , Carlos J. Suarez
    • , Shaukat Khan
    • , Kazuki Sawamoto
    • , Shunji Tomatsu
    • , Nitin Raj
    • , Laura D. Attardi
    • , Laure Aurelian
    •  & Matthew H. Porteus
  • Article
    | Open Access

    Thoracic aortic dissection has a high fatality rate and no effective treatment. Here, the authors develop cationic nanoparticles for the delivery of miR-145 and show that they stabilize vascular structures and prevent further deterioration of the aorta in mouse models of the disease.

    • Chen Xu
    • , Yanzhenzi Zhang
    • , Ke Xu
    • , Jing-Jun Nie
    • , Bingran Yu
    • , Sijin Li
    • , Gang Cheng
    • , Yulin Li
    • , Jie Du
    •  & Fu-Jian Xu
  • Article
    | Open Access

    The adaptor protein SHN3 suppresses new bone formation by controlling osteoblast activity. Here, the authors show that ablation of SHN3 function, either genetically or by delivering an artificial miRNA via AAV9, rescues bone loss in osteoporotic mice, and show that engineering of the AAV9 capsid improves targeting to bone

    • Yeon-Suk Yang
    • , Jun Xie
    • , Dan Wang
    • , Jung-Min Kim
    • , Phillip W. L. Tai
    • , Ellen Gravallese
    • , Guangping Gao
    •  & Jae-Hyuck Shim
  • Article
    | Open Access

    Synthetic promoters can be superior to native ones but the design is challenging without knowledge of gene regulation. Here the authors develop a pipeline that allows for screening a synthetic promoter library to identify high performance promoters in potentially any given cell state of interest.

    • Ming-Ru Wu
    • , Lior Nissim
    • , Doron Stupp
    • , Erez Pery
    • , Adina Binder-Nissim
    • , Karen Weisinger
    • , Casper Enghuus
    • , Sebastian R. Palacios
    • , Melissa Humphrey
    • , Zhizhuo Zhang
    • , Eva Maria Novoa
    • , Manolis Kellis
    • , Ron Weiss
    • , Samuel D. Rabkin
    • , Yuval Tabach
    •  & Timothy K. Lu
  • Article
    | Open Access

    Cochlear implant spectral resolution is limited by current spread from each stimulation electrode. Here the authors compare optogenetic, electric and acoustic stimulation in gerbils and demonstrate improved spectral resolution of optogenetic over conventional electric stimulation.

    • Alexander Dieter
    • , Carlos J. Duque-Afonso
    • , Vladan Rankovic
    • , Marcus Jeschke
    •  & Tobias Moser
  • Article
    | Open Access

    Adeno-associated viral vectors (AAV) are being developed for gene therapy of skeletal muscle, but it is a challenge to achieve robust gene expression. Here, the authors identify muscle-specific cisregulatory elements that lead to a substantial increase in micro-dystrophin and follistatin expression, resulting in a safe and sustainable rescue of the dystrophic phenotype in mouse models.

    • S. Sarcar
    • , W. Tulalamba
    • , M. Y. Rincon
    • , J. Tipanee
    • , H. Q. Pham
    • , H. Evens
    • , D. Boon
    • , E. Samara-Kuko
    • , M. Keyaerts
    • , M. Loperfido
    • , E. Berardi
    • , S. Jarmin
    • , P. In’t Veld
    • , G. Dickson
    • , T. Lahoutte
    • , M. Sampaolesi
    • , P. De Bleser
    • , T. VandenDriessche
    •  & M. K. Chuah
  • Article
    | Open Access

    The delivery of single therapeutic microRNAs in brain cancers is challenging. Here, the authors engineer three neuronal microRNAs (miR-124, 128 and 137) into a cluster that, targeting oncogenic chromatin repressors, increases survival of GBM-bearing mice when combined with chemotherapy.

    • Vivek Bhaskaran
    • , Michal O. Nowicki
    • , Mahmoud Idriss
    • , Miguel A. Jimenez
    • , Gianmarco Lugli
    • , Josie L. Hayes
    • , Ahmad Bakur Mahmoud
    • , Rachel E. Zane
    • , Carmela Passaro
    • , Keith L. Ligon
    • , Daphne Haas-Kogan
    • , Agnieszka Bronisz
    • , Jakub Godlewski
    • , Sean E. Lawler
    • , E. Antonio Chiocca
    •  & Pierpaolo Peruzzi
  • Article
    | Open Access

    Osteoarthritis (OA) is associated with cartilage degeneration, and no effective therapy exists. Here, the authors show that the HPIP protein modulates OA progression by regulating Wnt signaling, and that its knockdown in joints via AAV-mediated gene silencing attentuates pathology.

    • Quanbo Ji
    • , Xiaojie Xu
    • , Lei Kang
    • , Yameng Xu
    • , Jingbo Xiao
    • , Stuart B. Goodman
    • , Xiang Zhu
    • , Wenchao Li
    • , Juan Liu
    • , Xu Gao
    • , Zhifeng Yan
    • , Yuxuan Zheng
    • , Zheng Wang
    • , William J. Maloney
    • , Qinong Ye
    •  & Yan Wang
  • Article
    | Open Access

    Therapeutic genome engineering relies on the development of reliable, robust and versatile tools. Here the authors develop Cas9-Cas9 chimeras with high target site activity that generate predictable deletions.

    • Mehmet Fatih Bolukbasi
    • , Pengpeng Liu
    • , Kevin Luk
    • , Samantha F. Kwok
    • , Ankit Gupta
    • , Nadia Amrani
    • , Erik J. Sontheimer
    • , Lihua Julie Zhu
    •  & Scot A. Wolfe
  • Article
    | Open Access

    Immunogenicity of AAV vectors renders repeated AAV dosing ineffective. Here the authors show that coadministration of nanoparticle-encapsulated rapamycin overcomes AAV immunogenicity through Treg induction, enabling efficient AAV redosing in mice and nonhuman primates.

    • Amine Meliani
    • , Florence Boisgerault
    • , Romain Hardet
    • , Solenne Marmier
    • , Fanny Collaud
    • , Giuseppe Ronzitti
    • , Christian Leborgne
    • , Helena Costa Verdera
    • , Marcelo Simon Sola
    • , Severine Charles
    • , Alban Vignaud
    • , Laetitia van Wittenberghe
    • , Giorgia Manni
    • , Olivier Christophe
    • , Francesca Fallarino
    • , Christopher Roy
    • , Alicia Michaud
    • , Petr Ilyinskii
    • , Takashi Kei Kishimoto
    •  & Federico Mingozzi
  • Article
    | Open Access

    Cpf1 is a promising alternative to Cas9 though indel generation efficiency is target dependent. Here the authors show that the addition of a polyU 3′ overhang can improve the efficiency of low efficiency guide RNAs.

    • Su Bin Moon
    • , Jeong Mi Lee
    • , Jeong Gu Kang
    • , Nan-Ee Lee
    • , Dae-In Ha
    • , Do Yon Kim
    • , Sun Hee Kim
    • , Kwangsun Yoo
    • , Daesik Kim
    • , Jeong-Heon Ko
    •  & Yong-Sam Kim
  • Article
    | Open Access

    Patients with mutations in the ASL gene present with argininosuccinic aciduria characterised by hyperammonaemia and cognitive impairment. Here, the authors show that cerebral disease involves neuronal nitrosative/oxidative stress that is not induced by hyperammonaemia, and that it can be reversed using AAV-ASL directed to liver and brain in mice.

    • Julien Baruteau
    • , Dany P. Perocheau
    • , Joanna Hanley
    • , Maëlle Lorvellec
    • , Eridan Rocha-Ferreira
    • , Rajvinder Karda
    • , Joanne Ng
    • , Natalie Suff
    • , Juan Antinao Diaz
    • , Ahad A. Rahim
    • , Michael P. Hughes
    • , Blerida Banushi
    • , Helen Prunty
    • , Mariya Hristova
    • , Deborah A. Ridout
    • , Alex Virasami
    • , Simon Heales
    • , Stewen J. Howe
    • , Suzanne M. K. Buckley
    • , Philippa B. Mills
    • , Paul Gissen
    •  & Simon N. Waddington
  • Article
    | Open Access

    Suppression of gene expression due to aberrant promoter methylation contributes to organ fibrosis. Here, the authors couple a deactivated Cas9 to the TET3 catalytic domain to induce expression of four antifibrotic genes, and show that lentiviral-mediated delivery is effective in reducing kidney fibrosis in mouse models.

    • Xingbo Xu
    • , Xiaoying Tan
    • , Björn Tampe
    • , Tim Wilhelmi
    • , Melanie S. Hulshoff
    • , Shoji Saito
    • , Tobias Moser
    • , Raghu Kalluri
    • , Gerd Hasenfuss
    • , Elisabeth M. Zeisberg
    •  & Michael Zeisberg
  • Article
    | Open Access

    In vivo reprogramming of somatic cells is hampered by the need for vectors to express the OKSM factors in selected organs. Here the authors report new AAV-based vectors capable of in vivo reprogramming at low doses.

    • Elena Senís
    • , Lluc Mosteiro
    • , Stefan Wilkening
    • , Ellen Wiedtke
    • , Ali Nowrouzi
    • , Saira Afzal
    • , Raffaele Fronza
    • , Henrik Landerer
    • , Maria Abad
    • , Dominik Niopek
    • , Manfred Schmidt
    • , Manuel Serrano
    •  & Dirk Grimm
  • Article
    | Open Access

    The correction of genetic defects in utero could allow for improved outcomes of gene therapy. Here, the authors demonstrate safe delivery of nanoparticles to fetal mouse tissues, and show that nanoparticles containing peptide nucleic acids to edit the beta-globin gene are effective in a mouse model of beta-thalassemia.

    • Adele S. Ricciardi
    • , Raman Bahal
    • , James S. Farrelly
    • , Elias Quijano
    • , Anthony H. Bianchi
    • , Valerie L. Luks
    • , Rachael Putman
    • , Francesc López-Giráldez
    • , Süleyman Coşkun
    • , Eric Song
    • , Yanfeng Liu
    • , Wei-Che Hsieh
    • , Danith H. Ly
    • , David H. Stitelman
    • , Peter M. Glazer
    •  & W. Mark Saltzman
  • Article
    | Open Access

    RNA delivery for disease treatment often has low uptake efficiencies and cytotoxicity. Here the authors produce extracellular vesicles from red blood cells for in vivo cargo delivery.

    • Waqas Muhammad Usman
    • , Tin Chanh Pham
    • , Yuk Yan Kwok
    • , Luyen Tien Vu
    • , Victor Ma
    • , Boya Peng
    • , Yuen San Chan
    • , Likun Wei
    • , Siew Mei Chin
    • , Ajijur Azad
    • , Alex Bai-Liang He
    • , Anskar Y. H. Leung
    • , Mengsu Yang
    • , Ng Shyh-Chang
    • , William C. Cho
    • , Jiahai Shi
    •  & Minh T. N. Le
  • Article
    | Open Access

    The CRISPR endonuclease LbCpf1 is reported to have greater efficiency and specificity than Cas9. Here, the authors use LbCpf1 to target the angiogenesis-related genes VEGF and HIF1a, and show that delivery of the nuclease using AAV9 is effective in mouse models of macular degeneration.

    • Taeyoung Koo
    • , Sung Wook Park
    • , Dong Hyun Jo
    • , Daesik Kim
    • , Jin Hyoung Kim
    • , Hee-Yeon Cho
    • , Jeungeun Kim
    • , Jeong Hun Kim
    •  & Jin-Soo Kim
  • Article
    | Open Access

    The integration of exogenous DNA into the genome using CRISPR–Cas9 often presents a challenge to researchers. Here the authors fuse CtIP to Cas9 to stimulate recombination at target loci.

    • M. Charpentier
    • , A. H. Y. Khedher
    • , S. Menoret
    • , A. Brion
    • , K. Lamribet
    • , E. Dardillac
    • , C. Boix
    • , L. Perrouault
    • , L. Tesson
    • , S. Geny
    • , A. De Cian
    • , J. M. Itier
    • , I. Anegon
    • , B. Lopez
    • , C. Giovannangeli
    •  & J. P. Concordet
  • Article
    | Open Access

    Duchenne muscular dystrophy is a progressive degenerative disease of muscles caused by mutations in the dystrophin gene. Here the authors use AAV vectors to deliver microdystrophin to dogs with muscular dystrophy, and show restoration of dystrophin expression and reduction of symptoms up to 26 months of age.

    • Caroline Le Guiner
    • , Laurent Servais
    • , Marie Montus
    • , Thibaut Larcher
    • , Bodvaël Fraysse
    • , Sophie Moullec
    • , Marine Allais
    • , Virginie François
    • , Maeva Dutilleul
    • , Alberto Malerba
    • , Taeyoung Koo
    • , Jean-Laurent Thibaut
    • , Béatrice Matot
    • , Marie Devaux
    • , Johanne Le Duff
    • , Jack-Yves Deschamps
    • , Inès Barthelemy
    • , Stéphane Blot
    • , Isabelle Testault
    • , Karim Wahbi
    • , Stéphane Ederhy
    • , Samia Martin
    • , Philippe Veron
    • , Christophe Georger
    • , Takis Athanasopoulos
    • , Carole Masurier
    • , Federico Mingozzi
    • , Pierre Carlier
    • , Bernard Gjata
    • , Jean-Yves Hogrel
    • , Oumeya Adjali
    • , Fulvio Mavilio
    • , Thomas Voit
    • , Philippe Moullier
    •  & George Dickson
  • Article
    | Open Access

    Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.

    • Xionggao Huang
    • , Guohong Zhou
    • , Wenyi Wu
    • , Yajian Duan
    • , Gaoen Ma
    • , Jingyuan Song
    • , Ru Xiao
    • , Luk Vandenberghe
    • , Feng Zhang
    • , Patricia A. D’Amore
    •  & Hetian Lei
  • Article
    | Open Access

    Homologous recombination mediated gene targeting is highly inefficient in human cells due to random integration events, Here the authors show that dual repression of polymerase θ and DNA ligase IV eliminate random integration events.

    • Shinta Saito
    • , Ryo Maeda
    •  & Noritaka Adachi
  • Article
    | Open Access

    While CRISPR-Cas9 is a powerful technology, it’sin vivoapplication can be limited by unwanted off-target editing events. Here the authors present SLiCES, a self-limiting Cas9 circuit to enhance editing by preventing residual nuclease activity.

    • Gianluca Petris
    • , Antonio Casini
    • , Claudia Montagna
    • , Francesca Lorenzin
    • , Davide Prandi
    • , Alessandro Romanel
    • , Jacopo Zasso
    • , Luciano Conti
    • , Francesca Demichelis
    •  & Anna Cereseto
  • Article
    | Open Access

    Oculopharyngeal muscular dystrophy is caused by trinucleotide repeat expansions in thePABPN1gene. Here the authors use AAV-based gene therapy to knockdown the mutant gene and replace it with a wild-type allele, and show effectiveness in mice and in patient cells.

    • A. Malerba
    • , P. Klein
    • , H. Bachtarzi
    • , S. A. Jarmin
    • , G. Cordova
    • , A. Ferry
    • , V. Strings
    • , M. Polay Espinoza
    • , K. Mamchaoui
    • , S. C. Blumen
    • , J. Lacau St Guily
    • , V. Mouly
    • , M. Graham
    • , G. Butler-Browne
    • , D. A. Suhy
    • , C. Trollet
    •  & G. Dickson
  • Article
    | Open Access

    The maximum titre of therapeutic viral vectors can be adversely affected by the encoded transgene. Here the authors repress transgene expression in producing cells by employing the tryptophan RNA-binding attenuation protein and show that it improves titre of RNA- and DNA-based viral vectors expressing toxic transgenes.

    • H. E. Maunder
    • , J. Wright
    • , B. R. Kolli
    • , C. R. Vieira
    • , T. T. Mkandawire
    • , S. Tatoris
    • , V. Kennedy
    • , S. Iqball
    • , G. Devarajan
    • , S. Ellis
    • , Y. Lad
    • , N. G. Clarkson
    • , K. A. Mitrophanous
    •  & D. C. Farley
  • Article
    | Open Access

    Current methods for haematopoietic stem cell gene therapy are laborious and require special licensed facilities. Here the authors develop a semi-automated protocol using a commercially available device to allow for benchtop generation of gene-modified blood cell products for transplantation, that meet current standards.

    • Jennifer E. Adair
    • , Timothy Waters
    • , Kevin G. Haworth
    • , Sara P. Kubek
    • , Grant D. Trobridge
    • , Jonah D. Hocum
    • , Shelly Heimfeld
    •  & Hans-Peter Kiem
  • Article
    | Open Access

    Restoring lost excitability of injured tissue is a paramount of regenerative medicine. By using a combined expression of bacterial voltage-gated Na+ channel, Kir2.1, and connexin-43 in non-excitable human fibroblasts, here the authors generate excitable cells that rescue action potential conduction in an in vitromodel of cardiac fibrosis.

    • Hung X. Nguyen
    • , Robert D. Kirkton
    •  & Nenad Bursac
  • Article
    | Open Access

    Heart contraction, which is decreased in disease, is determined by Ca2+binding to troponin C. Here, the authors combine a protein engineering approach with gene therapy to modulate heart contractility in mice with the use of rationally designed Troponin C variants, suggesting a new therapy for diseased hearts.

    • Vikram Shettigar
    • , Bo Zhang
    • , Sean C. Little
    • , Hussam E. Salhi
    • , Brian J. Hansen
    • , Ning Li
    • , Jianchao Zhang
    • , Steve R. Roof
    • , Hsiang-Ting Ho
    • , Lucia Brunello
    • , Jessica K. Lerch
    • , Noah Weisleder
    • , Vadim V. Fedorov
    • , Federica Accornero
    • , Jill A. Rafael-Fortney
    • , Sandor Gyorke
    • , Paul M. L. Janssen
    • , Brandon J. Biesiadecki
    • , Mark T. Ziolo
    •  & Jonathan P. Davis
  • Article
    | Open Access

    Familial hypercholesterolemia (FH) is a congenital disease associated with high plasma cholesterol levels. Here, the authors recapitulate FH in chimeric mice, in which livers are repopulated with hepatocytes from an FH patient, and successfully correct the disease using adenovirus-mediated gene therapy.

    • Beatrice Bissig-Choisat
    • , Lili Wang
    • , Xavier Legras
    • , Pradip K. Saha
    • , Leon Chen
    • , Peter Bell
    • , Francis P. Pankowicz
    • , Matthew C. Hill
    • , Mercedes Barzi
    • , Claudia Kettlun Leyton
    • , Hon-Chiu Eastwood Leung
    • , Robert L. Kruse
    • , Ryan W. Himes
    • , John A. Goss
    • , James M. Wilson
    • , Lawrence Chan
    • , William R. Lagor
    •  & Karl-Dimiter Bissig
  • Article
    | Open Access

    The rd1 mouse is the most widely used model to study retinal degeneration. Here, the authors identify a wide-spread mutation in these mice that may explain the failure of previous gene therapeutic approaches and show that long-lasting restoration of vision is possible in rd1 mice without this mutation.

    • Koji M. Nishiguchi
    • , Livia S. Carvalho
    • , Matteo Rizzi
    • , Kate Powell
    • , Sophia-Martha kleine Holthaus
    • , Selina A. Azam
    • , Yanai Duran
    • , Joana Ribeiro
    • , Ulrich F. O. Luhmann
    • , James W. B. Bainbridge
    • , Alexander J. Smith
    •  & Robin R. Ali
  • Article |

    Hereditary hypertrophic cardiomyopathy (HCM) is caused by mutations in cardiomyocyte genes, such as MYBPC3. Here, the authors use virus-mediated gene therapy to correct Mycbpc3mutations in 1-day-old mice and, by administering just a single dose, prevent development of HCM over a period of 34 weeks.

    • Giulia Mearini
    • , Doreen Stimpel
    • , Birgit Geertz
    • , Florian Weinberger
    • , Elisabeth Krämer
    • , Saskia Schlossarek
    • , Julia Mourot-Filiatre
    • , Andrea Stoehr
    • , Alexander Dutsch
    • , Paul J. M. Wijnker
    • , Ingke Braren
    • , Hugo A. Katus
    • , Oliver J. Müller
    • , Thomas Voit
    • , Thomas Eschenhagen
    •  & Lucie Carrier
  • Article |

    The ‘funny’ current (If) is important for the generation and regulation of the heart’s automaticity. Here the authors show that If silencing through genetic modification of the f-channel component HCN4 causes heart arrhythmia by altering Ca2+handling in pacemaker myocytes.

    • Pietro Mesirca
    • , Jacqueline Alig
    • , Angelo G. Torrente
    • , Jana Christina Müller
    • , Laurine Marger
    • , Anne Rollin
    • , Claire Marquilly
    • , Anne Vincent
    • , Stefan Dubel
    • , Isabelle Bidaud
    • , Anne Fernandez
    • , Anika Seniuk
    • , Birgit Engeland
    • , Jasmin Singh
    • , Lucile Miquerol
    • , Heimo Ehmke
    • , Thomas Eschenhagen
    • , Joel Nargeot
    • , Kevin Wickman
    • , Dirk Isbrandt
    •  & Matteo E. Mangoni
  • Article
    | Open Access

    Haemophilia is a genetic bleeding disorder associated with a deficiency in the coagulation factor VIII. Here, the authors use gene therapy to achieve stable overexpression of factor VIII in platelets of dogs with haemophilia A, preventing the occurrence of severe bleeding episodes for over 2.5 years.

    • Lily M. Du
    • , Paquita Nurden
    • , Alan T. Nurden
    • , Timothy C. Nichols
    • , Dwight A. Bellinger
    • , Eric S. Jensen
    • , Sandra L. Haberichter
    • , Elizabeth Merricks
    • , Robin A. Raymer
    • , Juan Fang
    • , Sevasti B. Koukouritaki
    • , Paula M. Jacobi
    • , Troy B. Hawkins
    • , Kenneth Cornetta
    • , Qizhen Shi
    •  & David A. Wilcox
  • Article |

    Patient-specific induced pluripotent stem (iPS) cells hold great potential for regenerative cell therapies. Here Filareto et al. genetically correct iPS cells from mice with muscular dystrophy and use these cells to treat the same animals, providing a proof-of-principle for autologous iPS cell therapy.

    • Antonio Filareto
    • , Sarah Parker
    • , Radbod Darabi
    • , Luciene Borges
    • , Michelina Iacovino
    • , Tory Schaaf
    • , Timothy Mayerhofer
    • , Jeffrey S. Chamberlain
    • , James M. Ervasti
    • , R. Scott McIvor
    • , Michael Kyba
    •  & Rita C. R. Perlingeiro