Gene delivery

  • Article
    | Open Access

    Progressive familial intrahepatic cholestasis type 3 is a disease caused by mutations in the gene encoding the multidrug resistance protein 3, and has limited treatment options. Here they show that adeno-associated virus mediated gene therapy prevents disease progression in a mouse disease model.

    • Nicholas D. Weber
    • , Leticia Odriozola
    • , Javier Martínez-García
    • , Veronica Ferrer
    • , Anne Douar
    • , Bernard Bénichou
    • , Gloria González-Aseguinolaza
    •  & Cristian Smerdou
  • Article
    | Open Access

    Most reagents designed to deliver cargo into cells are cationic and so cannot deliver cationic cargo. Here the authors show that pretreating cells with the anionic polymer poly(propylacrylic acid) facilitates the uptake and endosomal escape of a wide variety of cationic cargo in numerous cell types.

    • Brian C. Evans
    • , R. Brock Fletcher
    • , Kameron V. Kilchrist
    • , Eric A. Dailing
    • , Alvin J. Mukalel
    • , Juan M. Colazo
    • , Matthew Oliver
    • , Joyce Cheung-Flynn
    • , Colleen M. Brophy
    • , John W. Tierney
    • , Jeffrey S. Isenberg
    • , Kurt D. Hankenson
    • , Kedar Ghimire
    • , Cynthia Lander
    • , Charles A. Gersbach
    •  & Craig L. Duvall
  • Article
    | Open Access

    Selectable markers are widely used in cell engineering but there is only a limited variety to choose from. Here the authors split markers using inteins, allowing up to six transgene integration events to be selected for with one marker.

    • Nathaniel Jillette
    • , Menghan Du
    • , Jacqueline Jufen Zhu
    • , Peter Cardoz
    •  & Albert Wu Cheng
  • Article
    | Open Access

    Lipid nanoparticles (LNPs) are potential platforms for RNA-based therapeutics, but the fate of LNP-RNAs upon internalization into the cell is unclear. Here, the authors show that LNP-mRNAs and ionizable lipids escape the endosomes and are re-released via extracellular vesicles which could deliver the functional mRNA to other cells.

    • Marco Maugeri
    • , Muhammad Nawaz
    • , Alexandros Papadimitriou
    • , Annelie Angerfors
    • , Alessandro Camponeschi
    • , Manli Na
    • , Mikko Hölttä
    • , Pia Skantze
    • , Svante Johansson
    • , Martina Sundqvist
    • , Johnny Lindquist
    • , Tomas Kjellman
    • , Inga-Lill Mårtensson
    • , Tao Jin
    • , Per Sunnerhagen
    • , Sofia Östman
    • , Lennart Lindfors
    •  & Hadi Valadi
  • Article
    | Open Access

    There are currently few AAV vectors that can effectively target the diverse cell types of the inner ear. Here the authors design AAV-ie for gene delivery to the mouse cochlea, targeting cochlear supporting cells.

    • Fangzhi Tan
    • , Cenfeng Chu
    • , Jieyu Qi
    • , Wenyan Li
    • , Dan You
    • , Ke Li
    • , Xin Chen
    • , Weidong Zhao
    • , Cheng Cheng
    • , Xiaoyi Liu
    • , Yunbo Qiao
    • , Bing Su
    • , Shuijin He
    • , Chao Zhong
    • , Huawei Li
    • , Renjie Chai
    •  & Guisheng Zhong
  • Article
    | Open Access

    Anaerobic bacteria represent a rich source of biological and chemical diversity but are difficult to cultivate and there is a lack of heterologous expression systems. Here the authors develop an expression system based on S. mutans UA159 for biosynthetic gene clusters from anaerobic bacteria.

    • Tingting Hao
    • , Zhoujie Xie
    • , Min Wang
    • , Liwei Liu
    • , Yuwei Zhang
    • , Weicang Wang
    • , Zhao Zhang
    • , Xuejin Zhao
    • , Pengwei Li
    • , Zhengyan Guo
    • , Shushan Gao
    • , Chunbo Lou
    • , Guodong Zhang
    • , Justin Merritt
    • , Geoff P. Horsman
    •  & Yihua Chen
  • Article
    | Open Access

    Mutations in the mechanotransduction channel component TMC1/2 cause deafness. Here, the authors use a synthetic AAV to replace TMC1 and 2 in the inner ear and show restoration of cochlear and vestibular function, of neuronal reponses in the auditory cortex and of hearing and balance in mice.

    • Carl A. Nist-Lund
    • , Bifeng Pan
    • , Amy Patterson
    • , Yukako Asai
    • , Tianwen Chen
    • , Wu Zhou
    • , Hong Zhu
    • , Sandra Romero
    • , Jennifer Resnik
    • , Daniel B. Polley
    • , Gwenaelle S. Géléoc
    •  & Jeffrey R. Holt
  • Article
    | Open Access

    Natural genetic transformation in bacteria requires DNA binding at the surface of competent cells. Here, Mirouze et al. show that wall teichoic acids are specifically produced or modified during competence in Bacillus subtilis and promote (directly or indirectly) DNA binding at the cell surface.

    • Nicolas Mirouze
    • , Cécile Ferret
    • , Charlène Cornilleau
    •  & Rut Carballido-López
  • Article
    | Open Access

    Interfering RNA have a range of therapeutic and research based applications, issues with delivery have made systems that make siRNA in situ of interest. Here, the author report on the creation of a DNA hydrogel with improved stability and transcription efficiency over plasmid DNA.

    • Jaejung Song
    • , Minhyuk Lee
    • , Taeyoung Kim
    • , Jeongkyeong Na
    • , Yebin Jung
    • , Gyoo Yeol Jung
    • , Sungjee Kim
    •  & Nokyoung Park
  • 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

    Activation of the NLRP3 inflammasome triggers the production of inflammatory cytokines. Here, the authors inactivate NLRP3 in macrophages using CRISPR/Cas9 encapsulated in nanoparticles, and show that administration in mice is effective in preventing septic shock and peritonitis, and in improving diabetes-associated inflammation and insulin resistance.

    • Congfei Xu
    • , Zidong Lu
    • , Yingli Luo
    • , Yang Liu
    • , Zhiting Cao
    • , Song Shen
    • , Hongjun Li
    • , Jing Liu
    • , Kaige Chen
    • , Zhiyao Chen
    • , Xianzhu Yang
    • , Zhen Gu
    •  & Jun Wang
  • Article
    | Open Access

    Single-particle cryo-EM is a powerful method for macromolecular structure determination. Here the authors demonstrate that Ewald sphere curvature correction, sub-Angstrom pixilation and per-particle CTF refinement can improve map quality and resolution and present the 1.86 Å cryo-EM structure of an adeno-associated virus serotype 2 variant.

    • Yong Zi Tan
    • , Sriram Aiyer
    • , Mario Mietzsch
    • , Joshua A. Hull
    • , Robert McKenna
    • , Joshua Grieger
    • , R. Jude Samulski
    • , Timothy S. Baker
    • , Mavis Agbandje-McKenna
    •  & Dmitry Lyumkis
  • Article
    | Open Access

    Classic monodirectional promoters are of limited use for multiple gene co-expression. Here the authors generate a library of 168 bidirectional promoters for the yeast K. phaffii (syn. P. pastoris) with diverse expression profiles to optimize metabolic pathway design.

    • Thomas Vogl
    • , Thomas Kickenweiz
    • , Julia Pitzer
    • , Lukas Sturmberger
    • , Astrid Weninger
    • , Bradley W. Biggs
    • , Eva-Maria Köhler
    • , Armin Baumschlager
    • , Jasmin Elgin Fischer
    • , Patrick Hyden
    • , Marlies Wagner
    • , Martina Baumann
    • , Nicole Borth
    • , Martina Geier
    • , Parayil Kumaran Ajikumar
    •  & Anton Glieder
  • Article
    | Open Access

    Novel therapeutic strategies are needed to improve the treatment outcome of hepatocellular carcinoma. Here, the authors develop a theranostical targeted nanomedicine platform that reveals the key oncogenic role of PBOV1 in hepatocellular carcinoma.

    • Yu Guo
    • , Zhiqiang Wu
    • , Shunli Shen
    • , Ruomi Guo
    • , Jing Wang
    • , Weiwei Wang
    • , Kun Zhao
    • , Ming Kuang
    •  & Xintao Shuai
  • Article
    | Open Access

    X-ray radiation has excellent tissue penetration depth, making it a useful trigger for deep tissue cancer therapy. Here, the authors design X-ray triggered drug/gene-loaded liposomes by embedding photosensitizers and gold nanoparticles in the liposome bilayer, and demonstrate their efficacy in cancer and gene therapy.

    • Wei Deng
    • , Wenjie Chen
    • , Sandhya Clement
    • , Anna Guller
    • , Zhenjun Zhao
    • , Alexander Engel
    •  & Ewa M. Goldys
  • 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

    In the context of increasing bacterial antibiotic-resistance, gene therapy that targets the immune system to clear infection is a major goal. Here the authors show a silicon based nanosystem that modulates the macrophage response in an in vivo model of Staphylococcal pneumonia.

    • Byungji Kim
    • , Hong-Bo Pang
    • , Jinyoung Kang
    • , Ji-Ho Park
    • , Erkki Ruoslahti
    •  & Michael J. Sailor
  • Article
    | Open Access

    Delivery of therapeutic proteins to patients may be costly to administer, and often requires repeated injections. Here, the authors use antigen-specific T cells expressing erythropoietin, and show that following transfer in mice, cell expansion and erythropoietin production can be boosted by vaccination, raising the haematocrit.

    • Richard T. O’Neil
    • , Sunandan Saha
    • , Ruth Ann Veach
    • , Richard C. Welch
    • , Lauren E. Woodard
    • , Cliona M. Rooney
    •  & Matthew H. Wilson
  • Article
    | Open Access

    Non-viral vectors are important for transfection but can be limited in the uptake, protection and release of ssDNA. Here, the authors report on the design of metal-organic-framework vectors with precisely controlled pore geometry and demonstrate the vector in the transfection of immune cells.

    • Shuang Peng
    • , Binglin Bie
    • , Yangzesheng Sun
    • , Min Liu
    • , Hengjiang Cong
    • , Wentao Zhou
    • , Yucong Xia
    • , Heng Tang
    • , Hexiang Deng
    •  & Xiang Zhou
  • Article
    | Open Access

    Viral gene therapy can be limited by the efficacy of virion sequestration, immune responses and the silencing of genetic payloads. Here the authors engineer an advenovirus protein coat which shields the virion from the immune system while targeting cancer cells.

    • Markus Schmid
    • , Patrick Ernst
    • , Annemarie Honegger
    • , Maarit Suomalainen
    • , Martina Zimmermann
    • , Lukas Braun
    • , Sarah Stauffer
    • , Cristian Thom
    • , Birgit Dreier
    • , Matthias Eibauer
    • , Anja Kipar
    • , Viola Vogel
    • , Urs F. Greber
    • , Ohad Medalia
    •  & Andreas Plückthun
  • Article
    | Open Access

    The pathogenesis of osteoarthritis is unclear. The authors show that estrogen-related receptor gamma is upregulated in cartilage from patients and mouse models, where it drives production of matrix-degrading MMPs in chondrocytes, and that its downregulation ameliorates pathology in mice.

    • Young-Ok Son
    • , Seulki Park
    • , Ji-Sun Kwak
    • , Yoonkyung Won
    • , Wan-Su Choi
    • , Jinseol Rhee
    • , Churl-Hong Chun
    • , Je-Hwang Ryu
    • , Don-Kyu Kim
    • , Hueng-Sik Choi
    •  & Jang-Soo Chun
  • Article
    | Open Access

    Current widely used viral and electroporation methods for creating therapeutic cell-based products are complex and expensive. Here, the authors develop targeted mRNA nanocarriers that can transiently program gene expression by simply mixing them with cells, to improve their therapeutic potential.

    • H. F. Moffett
    • , M. E. Coon
    • , S. Radtke
    • , S. B. Stephan
    • , L. McKnight
    • , A. Lambert
    • , B. L. Stoddard
    • , H. P. Kiem
    •  & M. T. Stephan
  • Article
    | Open Access

    Proliferation of synoviocytes contributes to joint damage in rheumatoid arthritis. Here the authors show that targeting of these cells by a vector, consisting of a baculovirus conjugated to an adenovirus carrying the pro-apoptotic gene PUMA, has therapeutic efficacy in a rat arthritis model.

    • Saw-See Hong
    • , Hubert Marotte
    • , Guillaume Courbon
    • , Gary S. Firestein
    • , Pierre Boulanger
    •  & Pierre Miossec
  • Article
    | Open Access

    Single-cell characterization and perturbation of neurons is critical for revealing the structure-function relationship of brain cells. Here the authors develop a robot that performs single-cell electroporation and extracellular electrophysiology and can be used for performingin vivosingle-cell experiments in deep brain tissues optically difficult to access.

    • Lu Li
    • , Benjamin Ouellette
    • , William A. Stoy
    • , Emma J. Garren
    • , Tanya L. Daigle
    • , Craig R. Forest
    • , Christof Koch
    •  & Hongkui Zeng
  • 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

    Uptake and integration of exogenous DNA into the bacterial genome play an important role in the evolution of the pathogen Helicobacter pylori. Here, the authors describe a bimodal pattern of chromosomal integration and show how restriction-modification systems limit the import of heterologous DNA.

    • Sebastian Bubendorfer
    • , Juliane Krebes
    • , Ines Yang
    • , Elias Hage
    • , Thomas F. Schulz
    • , Christelle Bahlawane
    • , Xavier Didelot
    •  & Sebastian Suerbaum
  • Article
    | Open Access

    The anti-diabetic drug Metformin also possesses anti-tumour activity. Here, the authors synthesize polymeric Metformin-based nanoparticles that still exert intrinsic biological activity through AMPK and mTOR regulation and can systematically deliver VEGF siRNA, significantly reducing lung cancer growth in mice.

    • Yi Zhao
    • , Wei Wang
    • , Shutao Guo
    • , Yuhua Wang
    • , Lei Miao
    • , Yang Xiong
    •  & Leaf Huang
  • Article
    | Open Access

    Current viral gene delivery systems are limited in the amount of foreign DNA they can deliver to cells. Here the authors develop MultiPrime, a baculovirus-based vector system capable of multigene delivery into a wide variety of cells, and use Multiprime for genome engineering by CRISPR/Cas9.

    • Maysam Mansouri
    • , Itxaso Bellon-Echeverria
    • , Aurélien Rizk
    • , Zahra Ehsaei
    • , Chiara Cianciolo Cosentino
    • , Catarina S. Silva
    • , Ye Xie
    • , Frederick M. Boyce
    • , M. Wayne Davis
    • , Stephan C. F. Neuhauss
    • , Verdon Taylor
    • , Kurt Ballmer-Hofer
    • , Imre Berger
    •  & Philipp Berger
  • Article
    | Open Access

    Algae hold great promise for biofuel and chemical production but their use as model systems is hampered by the absence of suitable genetic tools. Here Karas et al. present a nuclear episomal vector for diatoms that is maintained in the absence of antibiotics, and a plasmid delivery method via conjugation with E. coli.

    • Bogumil J. Karas
    • , Rachel E. Diner
    • , Stephane C. Lefebvre
    • , Jeff McQuaid
    • , Alex P.R. Phillips
    • , Chari M. Noddings
    • , John K. Brunson
    • , Ruben E. Valas
    • , Thomas J. Deerinck
    • , Jelena Jablanovic
    • , Jeroen T.F. Gillard
    • , Karen Beeri
    • , Mark H. Ellisman
    • , John I. Glass
    • , Clyde A. Hutchison III
    • , Hamilton O. Smith
    • , J. Craig Venter
    • , Andrew E. Allen
    • , Christopher L. Dupont
    •  & Philip D. Weyman
  • Article
    | Open Access

    Alterations of p53 are associated with more than half of all human cancers. Here the authors present a new pH-sensitive nanoparticle that is delivered via systemic circulation and combines gene delivery to restore p53 with expression of Killerred protein to induce photosensitization.

    • S.-Ja Tseng
    • , Zi-Xian Liao
    • , Shih-Han Kao
    • , Yi-Fang Zeng
    • , Kuo-Yen Huang
    • , Hsin-Jung Li
    • , Chung-Lin Yang
    • , Yu-Fan Deng
    • , Chi-Feng Huang
    • , Shuenn-Chen Yang
    • , Pan-Chyr Yang
    •  & Ivan M. Kempson
  • Article |

    The clinical use of adeno-associated virus vectors (AAVs) has been limited by the lack of transduction specificity. Here the authors show that receptor-targeted, affinity-tagged, and purified AVVs reach tumours in mouse models with high selectivity and efficiency, outperforming therapeutic antibodies.

    • Robert C. Münch
    • , Anke Muth
    • , Alexander Muik
    • , Thorsten Friedel
    • , Julia Schmatz
    • , Birgit Dreier
    • , Alexandra Trkola
    • , Andreas Plückthun
    • , Hildegard Büning
    •  & Christian J. Buchholz
  • Article |

    FadR is a regulator of fatty acid metabolism in bacteria, and contains a binding site for acyl-CoA. Here, Shi et al. present a structure of V. cholerae FadR and show that a unique C-terminal extension comprises a second acyl-CoA binding site, perhaps rendering V. choleraeFadR a more efficient regulator.

    • Wei Shi
    • , Gabriela Kovacikova
    • , Wei Lin
    • , Ronald K. Taylor
    • , Karen Skorupski
    •  & F. Jon Kull
  • Article |

    The incorporation of foreign objects into cells can be used in various avenues of biological research, although crossing the cell membrane can be challenging. Here, the authors use a diamond nanoneedle array for enhanced delivery of various particles into cells, including neurons.

    • Ying Wang
    • , Yang Yang
    • , Li Yan
    • , So Ying Kwok
    • , Wei Li
    • , Zhigang Wang
    • , Xiaoyue Zhu
    • , Guangyu Zhu
    • , Wenjun Zhang
    • , Xianfeng Chen
    •  & Peng Shi
  • Article |

    Robust and reliable structure–function relationships are valuable for the development of potent drug delivery systems. Here, the authors use a library of lipid-like materials to predict in vivosiRNA delivery efficacy without any biological testing.

    • Kathryn A. Whitehead
    • , J. Robert Dorkin
    • , Arturo J. Vegas
    • , Philip H. Chang
    • , Omid Veiseh
    • , Jonathan Matthews
    • , Owen S. Fenton
    • , Yunlong Zhang
    • , Karsten T. Olejnik
    • , Volkan Yesilyurt
    • , Delai Chen
    • , Scott Barros
    • , Boris Klebanov
    • , Tatiana Novobrantseva
    • , Robert Langer
    •  & Daniel G. Anderson
  • Article |

    Light-controlled mechanisms for the delivery of drug molecules to cells is a promising route for non-invasive disease therapy. Here, the authors develop a photosensitive polymeric micelle for light-induced gene transfection and show its effectiveness in vivovia systemic administration.

    • Takahiro Nomoto
    • , Shigeto Fukushima
    • , Michiaki Kumagai
    • , Kaori Machitani
    • , Arnida
    • , Yu Matsumoto
    • , Makoto Oba
    • , Kanjiro Miyata
    • , Kensuke Osada
    • , Nobuhiro Nishiyama
    •  & Kazunori Kataoka
  • Article
    | Open Access

    Clostridium difficile produces potent toxins that are encoded by its pathogenicity locus. Here, Brouwer et al. demonstrate surprising bacterial genome plasticity whereby the pathogenicity locus is transferred from toxigenic to non-toxigenic strains of C. difficileby conjugational transfer.

    • Michael S.M. Brouwer
    • , Adam P. Roberts
    • , Haitham Hussain
    • , Rachel J. Williams
    • , Elaine Allan
    •  & Peter Mullany
  • Article
    | Open Access

    Arginine-rich peptides act as delivery systems for the internalization of cargoes in cells. Here, the clustering of arginine units in a parallel array on a macrocyclic scaffold produces a vector with high efficiency in DNA delivery and transfection.

    • Valentina Bagnacani
    • , Valentina Franceschi
    • , Michele Bassi
    • , Michela Lomazzi
    • , Gaetano Donofrio
    • , Francesco Sansone
    • , Alessandro Casnati
    •  & Rocco Ungaro
  • Article
    | Open Access

    In uteroelectroporation allows the labelling of specific populations of neurons in the developing mouse brain. The authors of this paper present a simple modification of this method that increases labelling efficiency and allows, for the first time, transfection of Purkinje cells in the rat cerebellum.

    • Marco dal Maschio
    • , Diego Ghezzi
    • , Guillaume Bony
    • , Alessandro Alabastri
    • , Gabriele Deidda
    • , Marco Brondi
    • , Sebastian Sulis Sato
    • , Remo Proietti Zaccaria
    • , Enzo Di Fabrizio
    • , Gian Michele Ratto
    •  & Laura Cancedda
  • Article |

    Fluorescent proteins are widely used in molecular biology to visualize protein expression and localization. Here, Krizet al. describe an efficient and flexible modular plasmid-based eukaryotic expression cloning strategy for the homogeneous expression of several fluorescent proteins in one cell.

    • Andrijana Kriz
    • , Katharina Schmid
    • , Nadia Baumgartner
    • , Urs Ziegler
    • , Imre Berger
    • , Kurt Ballmer-Hofer
    •  & Philipp Berger