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

    RNA-seq is a powerful tool to investigate how drugs affect the transcriptome but library construction can be costly. Here the authors introduce DRUG-seq, an automated platform for high-throughput transcriptome profiling.

    • Chaoyang Ye
    • , Daniel J. Ho
    • , Marilisa Neri
    • , Chian Yang
    • , Tripti Kulkarni
    • , Ranjit Randhawa
    • , Martin Henault
    • , Nadezda Mostacci
    • , Pierre Farmer
    • , Steffen Renner
    • , Robert Ihry
    • , Leandra Mansur
    • , Caroline Gubser Keller
    • , Gregory McAllister
    • , Marc Hild
    • , Jeremy Jenkins
    •  &  Ajamete Kaykas
  • Nature Communications | Article | open

    Predicting the response to chemotherapy is a major goal of cancer research. Here the authors use CRISPR knockout screens in pancreatic ductal adenocarcinoma cells to identify deletions synergistic with MEK inhibitors.

    • Karol Szlachta
    • , Cem Kuscu
    • , Turan Tufan
    • , Sara J. Adair
    • , Stephen Shang
    • , Alex D. Michaels
    • , Matthew G. Mullen
    • , Natasha Lopes Fischer
    • , Jiekun Yang
    • , Limin Liu
    • , Prasad Trivedi
    • , Edward B. Stelow
    • , P. Todd Stukenberg
    • , J. Thomas Parsons
    • , Todd W. Bauer
    •  &  Mazhar Adli
  • Nature Communications | Article | open

    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
  • Nature Communications | Article | open

    Undesired off-target effects can hamper the use of CRISPR-Cas9 in therapeutic applications. Here the authors use a directed evolution approach to develop Sniper-Cas9 which combines high specificity with no loss of on-target activity.

    • Jungjoon K. Lee
    • , Euihwan Jeong
    • , Joonsun Lee
    • , Minhee Jung
    • , Eunji Shin
    • , Young-hoon Kim
    • , Kangin Lee
    • , Inyoung Jung
    • , Daesik Kim
    • , Seokjoong Kim
    •  &  Jin-Soo Kim
  • Nature Communications | Article | open

    CRISPR-guided cytidine deaminases, including BE3 (Base Editor 3) and Target-AID (activation-induced cytidine deaminase), can covert C:G base pairs to T:A at target site. Here, the authors generate missense mutations of mouse Psen1 gene and find BE3 has higher editing efficiency than Target-AID.

    • Hiroki Sasaguri
    • , Kenichi Nagata
    • , Misaki Sekiguchi
    • , Ryo Fujioka
    • , Yukio Matsuba
    • , Shoko Hashimoto
    • , Kaori Sato
    • , Deepika Kurup
    • , Takanori Yokota
    •  &  Takaomi C. Saido

Francesco Conti

  • Nature Communications | Article | open

    Osteoclasts mediate bone disruption in a number of degenerative bone diseases. Here, the authors show that miR-182 regulates osteoclastogenesis via PKR and IFN-beta signaling, is correlated with rheumatoid arthritis, and that its ablation or inhibition is protective against bone erosion in mouse models of osteoporosis or inflammatory arthritis.

    • Kazuki Inoue
    • , Zhonghao Deng
    • , Yufan Chen
    • , Eugenia Giannopoulou
    • , Ren Xu
    • , Shiaoching Gong
    • , Matthew B. Greenblatt
    • , Lingegowda S. Mangala
    • , Gabriel Lopez-Berestein
    • , David G. Kirsch
    • , Anil K. Sood
    • , Liang Zhao
    •  &  Baohong Zhao
  • Nature Communications | Article | open

    The regenerative capacity of muscle stem cells is impaired in Duchenne muscular dystrophy (DMD). Here, the authors show that the endocannabinoid receptor CB1 is activated by PAX7 in muscle stem cells, and that pharmacological inhibition of CB1 promotes stem cell activation and ameliorates symptoms in DMD mouse models.

    • Fabio A. Iannotti
    • , Ester Pagano
    • , Ombretta Guardiola
    • , Simone Adinolfi
    • , Valentina Saccone
    • , Silvia Consalvi
    • , Fabiana Piscitelli
    • , Elisabetta Gazzerro
    • , Giuseppe Busetto
    • , Diego Carrella
    • , Raffaele Capasso
    • , Pier Lorenzo Puri
    • , Gabriella Minchiotti
    •  &  Vincenzo Di Marzo
  • Nature Communications | Article | open

    Patients with myotonic dystrophy need to undergo invasive muscle biopsies to monitor disease progression and response to therapy. Here, the authors show that extracellular RNAs in human urine can be used as biomarkers to differentiate patients from unaffected controls, and to monitor exon skipping in patients with Duchenne muscular dystrophy taking the drug eteplirsen.

    • Layal Antoury
    • , Ningyan Hu
    • , Leonora Balaj
    • , Sudeshna Das
    • , Sofia Georghiou
    • , Basil Darras
    • , Tim Clark
    • , Xandra O. Breakefield
    •  &  Thurman M. Wheeler
  • Nature Communications | Article | open

    BMP promotes bone formation but its efficacy is limited in some patients. Here, the authors show that osteoporosis patients with a poor response to BMP have increased expression of Smurf1, which targets BMP effectors for degradation, and demonstrate that its chemical inhibition enhances BMP-mediated bone formation in mice.

    • Chao Liang
    • , Songlin Peng
    • , Jie Li
    • , Jun Lu
    • , Daogang Guan
    • , Feng Jiang
    • , Cheng Lu
    • , Fangfei Li
    • , Xiaojuan He
    • , Hailong Zhu
    • , D. W. T. Au
    • , Dazhi Yang
    • , Bao-Ting Zhang
    • , Aiping Lu
    •  &  Ge Zhang
  • Nature Communications | Article | open

    Endurance and resistance exercise have different effects on skeletal muscle phenotype. Using mouse models and human subjects, the authors show that JNK/Smad2 signaling acts as molecular switch that when activated by resistance exercise leads to hypertrophy, and when inhibited promotes endurance adaptations in muscle.

    • Sarah J. Lessard
    • , Tara L. MacDonald
    • , Prerana Pathak
    • , Myoung Sook Han
    • , Vernon G. Coffey
    • , Johann Edge
    • , Donato A. Rivas
    • , Michael F. Hirshman
    • , Roger J. Davis
    •  &  Laurie J. Goodyear

Sonja Schmid

  • Nature Communications | Article | open

    Eradication of bacterial infections can be hindered by poor penetration of antibiotics through biofilms. Here, Teirlinck et al. show that laser-induced vapour nanobubbles formed around plasmonic nanoparticles can be used to locally disturb biofilm integrity and improve antibiotic diffusion.

    • Eline Teirlinck
    • , Ranhua Xiong
    • , Toon Brans
    • , Katrien Forier
    • , Juan Fraire
    • , Heleen Van Acker
    • , Nele Matthijs
    • , Riet De Rycke
    • , Stefaan C. De Smedt
    • , Tom Coenye
    •  &  Kevin Braeckmans
  • Nature Communications | Article | open

    Safety and efficacy remain important challenges for non-antiretroviral-based microbicides. Here, Derby et al. show that a Griffithsin-Carrageenan fast dissolving vaginal insert provides on-demand protection against SHIV infections in macaques, paving the way for the development of pre-exposure prophylaxis on-demand products.

    • Nina Derby
    • , Manjari Lal
    • , Meropi Aravantinou
    • , Larisa Kizima
    • , Patrick Barnable
    • , Aixa Rodriguez
    • , Manshun Lai
    • , Asa Wesenberg
    • , Shweta Ugaonkar
    • , Keith Levendosky
    • , Olga Mizenina
    • , Kyle Kleinbeck
    • , Jeffrey D. Lifson
    • , M. Melissa Peet
    • , Zachary Lloyd
    • , Michael Benson
    • , Walid Heneine
    • , Barry R O’Keefe
    • , Melissa Robbiani
    • , Elena Martinelli
    • , Brooke Grasperge
    • , James Blanchard
    • , Agegnehu Gettie
    • , Natalia Teleshova
    • , José A. Fernández-Romero
    •  &  Thomas M. Zydowsky
  • Nature Communications | Article | open

    Sexual forms of malaria parasites are responsible for transmission to the mosquito. Anti-malarial drug resistance remains a serious problem and requires advent of new drug therapies. Here, the authors present a high-throughput screen of potential antimalarial compounds, identifying seventeen drug-like molecules specifically targeting transmission.

    • Michael J. Delves
    • , Celia Miguel-Blanco
    • , Holly Matthews
    • , Irene Molina
    • , Andrea Ruecker
    • , Sabrina Yahiya
    • , Ursula Straschil
    • , Matthew Abraham
    • , María Luisa León
    • , Oliver J. Fischer
    • , Ainoa Rueda-Zubiaurre
    • , Jochen R. Brandt
    • , Álvaro Cortés
    • , Anna Barnard
    • , Matthew J. Fuchter
    • , Félix Calderón
    • , Elizabeth A. Winzeler
    • , Robert E. Sinden
    • , Esperanza Herreros
    • , Francisco J. Gamo
    •  &  Jake Baum
  • Nature Communications | Article | open

    Microbial genomes encode enzymes for biosynthesis of many uncharacterized peptides. Here, the authors screen over 7,300 bacterial genomes for potential biosynthesis of cationic non-ribosomal peptides, and identify two novel peptides with activities against antibiotic-resistant Gram-negative pathogens.

    • Yong-Xin Li
    • , Zheng Zhong
    • , Wei-Peng Zhang
    •  &  Pei-Yuan Qian
  • Nature Communications | Article | open

    Ferumoxytol is a nanoparticle formulation approved for systemic use to treat iron deficiency. Liu et al. show that topical use of ferumoxytol, in combination with low concentrations of H2O2, disrupts intractable oral biofilms and prevents tooth decay in vitro and in an animal model.

    • Yuan Liu
    • , Pratap C. Naha
    • , Geelsu Hwang
    • , Dongyeop Kim
    • , Yue Huang
    • , Aurea Simon-Soro
    • , Hoi-In Jung
    • , Zhi Ren
    • , Yong Li
    • , Sarah Gubara
    • , Faizan Alawi
    • , Domenick Zero
    • , Anderson T. Hara
    • , David P. Cormode
    •  &  Hyun Koo
  • Nature Communications | Article | open

    Antibiotic resistance is a major threat across the whole healthcare spectrum. Here, the authors report on the development of biodegradable guanidinium functionalized polycarbonates and demonstrate antimicrobial activity against drug resistant infections.

    • Willy Chin
    • , Guansheng Zhong
    • , Qinqin Pu
    • , Chuan Yang
    • , Weiyang Lou
    • , Paola Florez De Sessions
    • , Balamurugan Periaswamy
    • , Ashlynn Lee
    • , Zhen Chang Liang
    • , Xin Ding
    • , Shujun Gao
    • , Collins Wenhan Chu
    • , Simone Bianco
    • , Chang Bao
    • , Yen Wah Tong
    • , Weimin Fan
    • , Min Wu
    • , James L. Hedrick
    •  &  Yi Yan Yang

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