Focus |

Therapeutics

Welcome to the Nature Communications Editors’ Highlights webpage on therapeutics. Each month our editors select a small number of Articles recently published in Nature Communications that they believe are particularly interesting or important.

The aim is to provide a snapshot of some of the most exciting work published in the area of therapeutics at Nature Communications. Each editor handles a different area of this research, as described below:

Ross Cloney handles therapeutic biotechnology, including manuscripts that involve novel vectors, nanoparticles, synthetic biology and genome engineering approaches. 

Francesco Conti handles manuscripts on muscle and bone biology, gene therapy, therapeutics, preclinical and clinical studies.

Sonja Schmid handles manuscripts on antimicrobials, ranging from drug or biologic discovery and preclinical work to clinical studies and trials.

Aishwarya Sundaram handles manuscripts on cancer drug discovery, cancer therapy, nanotherapy, metastasis, and tumor models. 

Ross Cloney

  • Nature Communications | Article | open

    The genomic locations that can be targeted for editing by CRISPR are limited by the presence of the nuclease-specific PAM sequence. Here, the authors show PAM recognition can be expanded by replacing the key region in the PAM interaction domain of SaCas9 with the corresponding region of SaCas9 orthologs.

    • Dacheng Ma
    • , Zhimeng Xu
    • , Zhaoyu Zhang
    • , Xi Chen
    • , Xiangzhi Zeng
    • , Yiyang Zhang
    • , Tingyue Deng
    • , Mengfei Ren
    • , Zheng Sun
    • , Rui Jiang
    •  &  Zhen Xie
  • Nature Communications | Article | open

    The Cas12b family of CRISPR nucleases has been underutilized in mammalian cells due to the high temperature requirement of known members. Here the authors engineer BhCas12b to overcome this limitation for robust and specific genome editing applications in human cells.

    • Jonathan Strecker
    • , Sara Jones
    • , Balwina Koopal
    • , Jonathan Schmid-Burgk
    • , Bernd Zetsche
    • , Linyi Gao
    • , Kira S. Makarova
    • , Eugene V. Koonin
    •  &  Feng Zhang
  • Nature Communications | Article | open

    Adeno-associated virus is used in gene therapy in mouse models of hearing loss. Here the authors compare vectors and find AAV2.7m8 can infect cells in the inner ear with high efficiency.

    • Kevin Isgrig
    • , Devin S. McDougald
    • , Jianliang Zhu
    • , Hong Jun Wang
    • , Jean Bennett
    •  &  Wade W. Chien
  • Nature Communications | Article | open

    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

Francesco Conti

  • Nature Communications | Article | open

    Beta II protein kinase C (βIIPKC) activation contributes to heart failure. Here the authors show, in a rat model of myocardial infarction, that heart failure outcome can be improved by selectively inhibiting the interaction between βIIPKC and its downstream mitochondrial target Mitofusin-1, and that this strategy is superior to global βIIPKC inhibition.

    • Julio C. B. Ferreira
    • , Juliane C. Campos
    • , Nir Qvit
    • , Xin Qi
    • , Luiz H. M. Bozi
    • , Luiz R. G. Bechara
    • , Vanessa M. Lima
    • , Bruno B. Queliconi
    • , Marie-Helene Disatnik
    • , Paulo M. M. Dourado
    • , Alicia J. Kowaltowski
    •  &  Daria Mochly-Rosen
  • Nature Communications | Article | open

    Imbalanced proteostasis is associated with diverse diseases, including ischemia/reperfusion injury in the heart. Here the authors show that the ATF6 arm of the unfolded protein response can be pharmacologically activated with a small molecule in vivo, providing protection from ischemia/reperfusion injury in the heart, the brain, and the kidney.

    • Erik A. Blackwood
    • , Khalid Azizi
    • , Donna J. Thuerauf
    • , Ryan J. Paxman
    • , Lars Plate
    • , Jeffery W. Kelly
    • , R. Luke Wiseman
    •  &  Christopher C. Glembotski
  • Nature Communications | Article | open

    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
  • Nature Communications | Article | open

    Myotonic dystrophy type 1 (DM1) is associated with aberrant transcript splicing. Here, the authors develop a transgenic mouse model expressing a bi-chromatic reporter system that allows non-invasive monitoring of splicing of a transcript altered in DM1 in vivo, and show that it allows for evaluation of the therapeutic response to treatment with antisense oligonucleotides.

    • Ningyan Hu
    • , Layal Antoury
    • , Timothy M. Baran
    • , Soumya Mitra
    • , C. Frank Bennett
    • , Frank Rigo
    • , Thomas H. Foster
    •  &  Thurman M. Wheeler
  • Nature Communications | Article | open

    Myotubular myopathy is a severe muscle disease for which no effective treatment exists. Here, the authors show that tamoxifen ameliorates pathology and extends survival in a mouse model of the disease, and that the effect is mediated via estrogen receptor signaling and involves modulation of DNM2 expression.

    • Nika Maani
    • , Nesrin Sabha
    • , Kamran Rezai
    • , Arun Ramani
    • , Linda Groom
    • , Nadine Eltayeb
    • , Faranak Mavandadnejad
    • , Andrea Pang
    • , Giulia Russo
    • , Michael Brudno
    • , Volker Haucke
    • , Robert T. Dirksen
    •  &  James J. Dowling
  • Nature Communications | Article | open

    X-linked myotubular myopathy (XLMTM) is a severe muscle disease with no effective treatment. Here, the authors show that tamoxifen, a drug used to treat breast cancer, rescues the pathology in a mouse model of the disease, at least in part by normalizing expression of the disease modifier proteins DNM2 and BIN1

    • Elinam Gayi
    • , Laurence A. Neff
    • , Xènia Massana Muñoz
    • , Hesham M. Ismail
    • , Marta Sierra
    • , Thomas Mercier
    • , Laurent A. Décosterd
    • , Jocelyn Laporte
    • , Belinda S. Cowling
    • , Olivier M. Dorchies
    •  &  Leonardo Scapozza

Sonja Schmid

  • Nature Communications | Article | open

    Seasonal malaria chemoprevention provides substantial benefit for young children, but resistance to used drugs will likely develop. Here, Chotsiri et al. evaluate the use of dihydroartemisinin-piperaquine as a regimen in 179 children, and population-based simulations suggest that small children would benefit from a higher and extended dosage.

    • Palang Chotsiri
    • , Issaka Zongo
    • , Paul Milligan
    • , Yves Daniel Compaore
    • , Anyirékun Fabrice Somé
    • , Daniel Chandramohan
    • , Warunee Hanpithakpong
    • , François Nosten
    • , Brian Greenwood
    • , Philip J. Rosenthal
    • , Nicholas J. White
    • , Jean-Bosco Ouédraogo
    •  &  Joel Tarning
  • Nature Communications | Article | open

    Current experimental monoclonal antibodies (mAbs) for Ebola virus (EBOV) post-exposure immunotherapy are ineffective against Sudan (SUDV) or Marburg virus (MARV). Here, authors develop cocktails of mAbs that protect nonhuman primates against EBOV, SUDV, and MARV infection when given four days post infection.

    • Jennifer M. Brannan
    • , Shihua He
    • , Katie A. Howell
    • , Laura I. Prugar
    • , Wenjun Zhu
    • , Hong Vu
    • , Sergey Shulenin
    • , Shweta Kailasan
    • , Henna Raina
    • , Gary Wong
    • , Md Niaz Rahim
    • , Logan Banadyga
    • , Kevin Tierney
    • , Xuelian Zhao
    • , Yuxing Li
    • , Frederick W. Holtsberg
    • , John M. Dye
    • , Xiangguo Qiu
    •  &  M. Javad Aman
  • Nature Communications | Article | open

    Parasitic nematodes causing onchocerciasis and lymphatic filariasis rely on a bacterial endosymbiont, Wolbachia, which is a validated therapeutic target. Here, Clare et al. perform a high-throughput screen of 1.3 million compounds and identify 5 chemotypes with faster kill rates than existing anti-Wolbachia drugs.

    • Rachel H. Clare
    • , Catherine Bardelle
    • , Paul Harper
    • , W. David Hong
    • , Ulf Börjesson
    • , Kelly L. Johnston
    • , Matthew Collier
    • , Laura Myhill
    • , Andrew Cassidy
    • , Darren Plant
    • , Helen Plant
    • , Roger Clark
    • , Darren A. N. Cook
    • , Andrew Steven
    • , John Archer
    • , Paul McGillan
    • , Sitthivut Charoensutthivarakul
    • , Jaclyn Bibby
    • , Raman Sharma
    • , Gemma L. Nixon
    • , Barton E. Slatko
    • , Lindsey Cantin
    • , Bo Wu
    • , Joseph Turner
    • , Louise Ford
    • , Kirsty Rich
    • , Mark Wigglesworth
    • , Neil G. Berry
    • , Paul M. O’Neill
    • , Mark J. Taylor
    •  &  Stephen A. Ward
  • Nature Communications | Article | open

    Clostridium difficile causes diarrhea and colitis by producing up to three different protein toxins. Here, Tam et al. show that an anthelmintic drug, niclosamide, inhibits the pathogenesis of all three toxins by targeting a host process required for toxin entry into host cells, without disrupting the gut microbiota.

    • John Tam
    • , Therwa Hamza
    • , Bing Ma
    • , Kevin Chen
    • , Greg L. Beilhartz
    • , Jacques Ravel
    • , Hanping Feng
    •  &  Roman A. Melnyk
  • Nature Communications | Article | open

    HIV infected cells persist for decades in patients under ART, but the mechanisms responsible remain unclear. Here, Reeves et al. use modeling approaches adapted from ecology to show that cellular proliferation, rather than viral replication, generates a majority of infected cells during ART.

    • Daniel B. Reeves
    • , Elizabeth R. Duke
    • , Thor A. Wagner
    • , Sarah E. Palmer
    • , Adam M. Spivak
    •  &  Joshua T. Schiffer
  • Nature Communications | Article | open

    The Ebola virus glycoprotein is a target for cross-protective antibodies. Here, Janus et al. report the crystal structure of the antigen-binding fragment of a pan-reactive antibody bound to a conserved epitope of the glycoprotein, facilitating rational design of cross-protective vaccines and therapeutics.

    • Benjamin M. Janus
    • , Nydia van Dyk
    • , Xuelian Zhao
    • , Katie A. Howell
    • , Cinque Soto
    • , M. Javad Aman
    • , Yuxing Li
    • , Thomas R. Fuerst
    •  &  Gilad Ofek

Aishwarya Sundaram

  • Nature Communications | Article | open

    Chimeric antigen receptors (CARs) are effective tools for directing T cell killing of tumors, but may cause adverse side effects. Here the authors show that coupling of antigen-recognition and CD3-binding in a modular format induces more efficient anti-tumour responses but reduced toxicity when compared with current CARs.

    • Christopher W. Helsen
    • , Joanne A. Hammill
    • , Vivian W. C. Lau
    • , Kenneth A. Mwawasi
    • , Arya Afsahi
    • , Ksenia Bezverbnaya
    • , Lisa Newhook
    • , Danielle L. Hayes
    • , Craig Aarts
    • , Bojana Bojovic
    • , Galina F. Denisova
    • , Jacek M. Kwiecien
    • , Ian Brain
    • , Heather Derocher
    • , Katy Milne
    • , Brad H. Nelson
    •  &  Jonathan L. Bramson
  • Nature Communications | Article | open

    ARID1A is highly inactivated in cancer. Here, the authors show that ARID1A has a synthetic lethal interaction with AURKA in colorectal cancer cells and that ARID1A deficiency activates the AURKA target CDC25C, whose inhibitors also cause cell death in the ARID1A-deficient cell lines.

    • Changjie Wu
    • , Junfang Lyu
    • , Eun Ju Yang
    • , Yifan Liu
    • , Baoyuan Zhang
    •  &  Joong Sup Shim
  • Nature Communications | Article | open

    Temozolomide (TMZ) resistance in glioblastomas (GBM) is associated with increased MGMT expression. Here, the authors identify an enhancer between the promoters of MKI67 and MGMT, that when activated drives MGMT expression despite MGMT promoter methylation to confer TMZ resistance in GBM.

    • Xiaoyue Chen
    • , Minjie Zhang
    • , Haiyun Gan
    • , Heping Wang
    • , Jeong-Heon Lee
    • , Dong Fang
    • , Gaspar J. Kitange
    • , Lihong He
    • , Zeng Hu
    • , Ian F. Parney
    • , Fredric B. Meyer
    • , Caterina Giannini
    • , Jann N. Sarkaria
    •  &  Zhiguo Zhang
  • Nature Communications | Article | open

    Usually, several components are needed for efficient 2-photon photodynamic therapy (PDT). Here, the authors sandwiched carboxylic acids between layered double hydroxide nanosheets to obtain a single-handed biocompatible photosensitizer that generates singlet oxygen in high quantum yield.

    • Rui Gao
    • , Xuan Mei
    • , Dongpeng Yan
    • , Ruizheng Liang
    •  &  Min Wei
  • Nature Communications | Article | open

    Histone modifications in cancer can contribute to pathogenesis. Here, the authors demonstrate that targeting epigenetic modifier Ezh2 hinders metastatic behaviour in Luminal B breast cancer models, and highlight a mechanism where Ezh2 contributes to metastatic behaviour by repression of FOXC1.

    • Alison Hirukawa
    • , Harvey W. Smith
    • , Dongmei Zuo
    • , Catherine R. Dufour
    • , Paul Savage
    • , Nicholas Bertos
    • , Radia M. Johnson
    • , Tung Bui
    • , Guillaume Bourque
    • , Mark Basik
    • , Vincent Giguère
    • , Morag Park
    •  &  William J. Muller
  • Nature Communications | Article | open

    Synthetic lethality (SL) offers a new precision oncology approach, which is based on targeting cancer-specific vulnerabilities across the whole genome, going beyond cancer drivers. The authors develop an approach termed ISLE to identify clinically relevant SL interactions and use them for patient stratification and novel target identification.

    • Joo Sang Lee
    • , Avinash Das
    • , Livnat Jerby-Arnon
    • , Rand Arafeh
    • , Noam Auslander
    • , Matthew Davidson
    • , Lynn McGarry
    • , Daniel James
    • , Arnaud Amzallag
    • , Seung Gu Park
    • , Kuoyuan Cheng
    • , Welles Robinson
    • , Dikla Atias
    • , Chani Stossel
    • , Ella Buzhor
    • , Gidi Stein
    • , Joshua J. Waterfall
    • , Paul S. Meltzer
    • , Talia Golan
    • , Sridhar Hannenhalli
    • , Eyal Gottlieb
    • , Cyril H. Benes
    • , Yardena Samuels
    • , Emma Shanks
    •  &  Eytan Ruppin