Protein delivery

  • Article
    | Open Access

    Inefficient delivery of proteins into mammalian cells limits their use in research and therapy. Here, the authors discover that ProTα, a small, intrinsically disordered human protein can facilitate efficient cationic lipid-mediated protein delivery of genome editing proteins into mammalian cells.

    • Y. Bill Kim
    • , Kevin T. Zhao
    • , David B. Thompson
    •  & David R. Liu
  • Article
    | Open Access

    Lysosomal replacement enzymes are taken up by cell surface receptors that recognize glycans, the effects of different glycan features are unknown. Here the authors present a gene engineering screen in CHO cells that allows custom N-glycan-decorated enzymes with improved circulation time and organ distribution.

    • Weihua Tian
    • , Zilu Ye
    • , Shengjun Wang
    • , Morten Alder Schulz
    • , Julie Van Coillie
    • , Lingbo Sun
    • , Yen-Hsi Chen
    • , Yoshiki Narimatsu
    • , Lars Hansen
    • , Claus Kristensen
    • , Ulla Mandel
    • , Eric Paul Bennett
    • , Siamak Jabbarzadeh-Tabrizi
    • , Raphael Schiffmann
    • , Jin-Song Shen
    • , Sergey Y. Vakhrushev
    • , Henrik Clausen
    •  & Zhang Yang
  • Article
    | Open Access

    A current challenge in genome editing is delivering Cas9 and sgRNA into target cells. Here the authors engineer a delivery system based on murine leukemia virus-like particles loaded with Cas9-sgRNA ribonucleoproteins to induce efficient genome editing in both cell culture and in vivo in mouse.

    • Philippe E. Mangeot
    • , Valérie Risson
    • , Floriane Fusil
    • , Aline Marnef
    • , Emilie Laurent
    • , Juliana Blin
    • , Virginie Mournetas
    • , Emmanuelle Massouridès
    • , Thibault J. M. Sohier
    • , Antoine Corbin
    • , Fabien Aubé
    • , Marie Teixeira
    • , Christian Pinset
    • , Laurent Schaeffer
    • , Gaëlle Legube
    • , François-Loïc Cosset
    • , Els Verhoeyen
    • , Théophile Ohlmann
    •  & Emiliano P. Ricci
  • Article
    | Open Access

    Optimization of the recently discovered Class 2 CRISPR protein Cpf1 has the potential to promote its applications in gene editing and therapeutics. Here, the authors find that extending the 5′ end of the crRNA can increase both the editing efficiency and delivery of Cpf1 in vitro and in vivo.

    • Hyo Min Park
    • , Hui Liu
    • , Joann Wu
    • , Anthony Chong
    • , Vanessa Mackley
    • , Christof Fellmann
    • , Anirudh Rao
    • , Fuguo Jiang
    • , Hunghao Chu
    • , Niren Murthy
    •  & Kunwoo Lee
  • Article
    | Open Access

    Proteins can serve as means of medical treatment, but their efficient delivery to cells is difficult. Here, the authors present a type of polymers, fluoroamphiphiles, acting as chemical chaperones that can facilitate the import of proteins into the inner compartment, i.e. cytosol, of cells.

    • Zhenjing Zhang
    • , Wanwan Shen
    • , Jing Ling
    • , Yang Yan
    • , Jingjing Hu
    •  & Yiyun Cheng
  • Article
    | Open Access

    One of the challenges of biologic drug therapy is delivery into target cells and tissues. Here the authors present ARMMs (arrestin domain containing protein 1 mediated microvesicles) as a versatile platform for packaging and delivery of a myriad of molecules, including p53, RNAs and CRISPR-Cas9.

    • Qiyu Wang
    • , Jiujiu Yu
    • , Tatenda Kadungure
    • , Joseph Beyene
    • , Hong Zhang
    •  & Quan Lu
  • Article
    | Open Access

    Relatively well conserved domains of influenza A virus (IAV) proteins are potential candidates for the development of a universal IAV vaccine. Here, Deng et al. combine two such conserved antigens (M2e and HA stalk) in a double-layered protein nanoparticle and show that it protects against divergent IAVs in mice.

    • Lei Deng
    • , Teena Mohan
    • , Timothy Z. Chang
    • , Gilbert X. Gonzalez
    • , Ye Wang
    • , Young-Man Kwon
    • , Sang-Moo Kang
    • , Richard W. Compans
    • , Julie A. Champion
    •  & Bao-Zhong Wang
  • Article
    | Open Access

    Third-generation base editors consist of a catalytically disabled Cas9 fused to a cytidine deaminase and a base excision repair inhibitor, enabling efficient, precise editing of individual base pairs in DNA. Here the authors describe engineering and protein delivery of base editors to improve their DNA specificity and enable specific base editing in live animals.

    • Holly A. Rees
    • , Alexis C. Komor
    • , Wei-Hsi Yeh
    • , Joana Caetano-Lopes
    • , Matthew Warman
    • , Albert S. B. Edge
    •  & David R. Liu
  • Article
    | Open Access

    The depletion of antigen-specific, deleterious antibodies during therapy and diagnosis remains an unsolved challenge. Here the authors develop ‘Seldegs’, antigens linked to human Fc fragments with high affinity for the neonatal Fc receptor FcRn, to deplete MOG- and HER2-specific antibodies in mice.

    • Siva Charan Devanaboyina
    • , Priyanka Khare
    • , Dilip K. Challa
    • , Raimund J. Ober
    •  & E. Sally Ward
  • Article
    | Open Access

    The type III secretion system is a needle-like molecular machine under tight regulatory control. Here the authors construct a synthetic type III secretion system gene cluster by deconstructing and rebuilding the wild-typeSalmonellapathogenicity island 1.

    • Miryoung Song
    • , David J. Sukovich
    • , Luciano Ciccarelli
    • , Julia Mayr
    • , Jesus Fernandez-Rodriguez
    • , Ethan A. Mirsky
    • , Alex C. Tucker
    • , D. Benjamin Gordon
    • , Thomas C. Marlovits
    •  & Christopher A. Voigt
  • Article
    | Open Access

    Exosomes have been identified as promising vehicles for the in vivodelivery of therapeutic molecules. Here the authors design a system to load protein cargos into exosomes during their biogenesis using optogenetic control of protein-protein interactions between the cargo and an exosome-localized partner.

    • Nambin Yim
    • , Seung-Wook Ryu
    • , Kyungsun Choi
    • , Kwang Ryeol Lee
    • , Seunghee Lee
    • , Hojun Choi
    • , Jeongjin Kim
    • , Mohammed R. Shaker
    • , Woong Sun
    • , Ji-Ho Park
    • , Daesoo Kim
    • , Won Do Heo
    •  & Chulhee Choi
  • Article
    | Open Access

    Most of the cell penetrating peptides can transport therapeutic agents across plasma membranes but barely across the blood-brain barrier. Here the authors develop a peptide that can enter the brain, and show that its fusion to immunomodulatory protein ctCTLA-4 is effective in a mouse model of multiple sclerosis.

    • Sangho Lim
    • , Won-Ju Kim
    • , Yeon-Ho Kim
    • , Sohee Lee
    • , Ja-Hyun Koo
    • , Jung-Ah Lee
    • , Heeseok Yoon
    • , Do-Hyun Kim
    • , Hong-Jai Park
    • , Hye-Mi Kim
    • , Hong-Gyun Lee
    • , Ji Yun Kim
    • , Jae-Ung Lee
    • , Jae Hun Shin
    • , Lark Kyun Kim
    • , Junsang Doh
    • , Hongtae Kim
    • , Sang-Kyou Lee
    • , Alfred L. M. Bothwell
    • , Minah Suh
    •  & Je-Min Choi