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

    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
  • Nature Communications | Article | open

    A rigorous understanding of off-target effects is necessary for SaCas9 to be used in therapeutic genome editing. Here the authors measure SaCas9 mismatch tolerance across a pairwise library screen of 88,000 guides and targets in human cells and develop a model which ranks off-target sites.

    • Josh Tycko
    • , Luis A. Barrera
    • , Nicholas C. Huston
    • , Ari E. Friedland
    • , Xuebing Wu
    • , Jonathan S. Gootenberg
    • , Omar O. Abudayyeh
    • , Vic E. Myer
    • , Christopher J. Wilson
    •  &  Patrick D. Hsu
  • Nature Communications | Article | open

    Mimicking enzyme function and improving upon it is a challenge facing nanotechnology. Here the authors design a DNA nanostructure that catalyzes the transport of lipids between bilayers at a rate three orders of magnitude higher than biological enzymes.

    • Alexander Ohmann
    • , Chen-Yu Li
    • , Christopher Maffeo
    • , Kareem Al Nahas
    • , Kevin N. Baumann
    • , Kerstin Göpfrich
    • , Jejoong Yoo
    • , Ulrich F. Keyser
    •  &  Aleksei Aksimentiev
  • Nature Communications | Article | open

    The absence of effective gene activators in bacteria limits regulated expression programs. Here the authors design synthetic bacterial CRISPR-Cas transcriptional activators that can be used to construct multi-gene programs of activation and repression.

    • Chen Dong
    • , Jason Fontana
    • , Anika Patel
    • , James M. Carothers
    •  &  Jesse G. Zalatan

Francesco Conti

  • 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
  • Nature Communications | Article | open

    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
  • Nature Communications | Article | open

    Depletion of the splicing factors MBNL 1 and 2 causes myotonic dystrophy. Here, the authors show that miR-23b and miR-218 target MBNL proteins, and that antagonists to these miRNAs rescue mis-splicing events in myoblasts and boost MBNL expression and rescue pathology in mouse models.

    • Estefania Cerro-Herreros
    • , Maria Sabater-Arcis
    • , Juan M. Fernandez-Costa
    • , Nerea Moreno
    • , Manuel Perez-Alonso
    • , Beatriz Llamusi
    •  &  Ruben Artero
  • Nature Communications | Article | open

    Laminins are important regulators of epidermal wound healing. Here, the authors show that laminins bind to multiple growth factors via their heparin-binding domains, and that incorporation of these domains into fibrin matrices increases growth factor retention, promoting wound healing in type 2 diabetic mouse models.

    • Jun Ishihara
    • , Ako Ishihara
    • , Kazuto Fukunaga
    • , Koichi Sasaki
    • , Michael J. V. White
    • , Priscilla S. Briquez
    •  &  Jeffrey A. Hubbell
  • Nature Communications | Article | open

    Smooth muscle cells (SMCs) invade atherosclerotic lesions and expand, contributing to plaque progression. Here Misra et al. show that SMC-derived plaque cells come from a single SMC and integrin β3 in SMCs and macrophages regulate the fate, expansion and migration of SMCs during plaque formation.

    • Ashish Misra
    • , Zhonghui Feng
    • , Rachana R. Chandran
    • , Inamul Kabir
    • , Noemi Rotllan
    • , Binod Aryal
    • , Abdul Q. Sheikh
    • , Ling Ding
    • , Lingfeng Qin
    • , Carlos Fernández-Hernando
    • , George Tellides
    •  &  Daniel M. Greif
  • Nature Communications | Article | open

    Mutations that lead to misfolding of rhodopsin can cause retinitis pigmentosa. Here, the authors carry out a high throughput screen to identify a small molecule chaperone of rod opsin, and show that it protects mouse models of retinitis pigmentosa from retinal degeneration.

    • Yuanyuan Chen
    • , Yu Chen
    • , Beata Jastrzebska
    • , Marcin Golczak
    • , Sahil Gulati
    • , Hong Tang
    • , William Seibel
    • , Xiaoyu Li
    • , Hui Jin
    • , Yong Han
    • , Songqi Gao
    • , Jianye Zhang
    • , Xujie Liu
    • , Hossein Heidari-Torkabadi
    • , Phoebe L. Stewart
    • , William E. Harte
    • , Gregory P. Tochtrop
    •  &  Krzysztof Palczewski

Sonja Schmid

  • 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
  • Nature Communications | Article | open

    The authors show that antifungal tolerance, defined as the fraction of growth of a fungal pathogen above the minimal inhibitory concentration, is due to the slow growth of subpopulations of cells that overcome drug stress, and that high tolerance is often associated with persistent infections.

    • Alexander Rosenberg
    • , Iuliana V. Ene
    • , Maayan Bibi
    • , Shiri Zakin
    • , Ella Shtifman Segal
    • , Naomi Ziv
    • , Alon M. Dahan
    • , Arnaldo Lopes Colombo
    • , Richard J. Bennett
    •  &  Judith Berman
  • Nature Communications | Article | open

    A limited number of therapeutics is available to treat influenza A virus (IAV) infections. Here, the authors show that defective interfering genes, delivered with a dual-functional peptide that enables intracellular accumulation and prevents endosomal acidification, inhibit IAV replication in vitro and in vivo.

    • Hanjun Zhao
    • , Kelvin K. W. To
    • , Hin Chu
    • , Qiulu Ding
    • , Xiaoyu Zhao
    • , Cun Li
    • , Huiping Shuai
    • , Shuofeng Yuan
    • , Jie Zhou
    • , Kin-Hang Kok
    • , Shibo Jiang
    •  &  Kwok-Yung Yuen
  • Nature Communications | Article | open

    The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMX) synergistically inhibit bacterial tetrahydrofolate biosynthesis, apparently because SMX potentiates TMP activity. Here, Minato et al. identify a metabolic feedback loop in this pathway, revealing that TMP also potentiates SMX activity.

    • Yusuke Minato
    • , Surendra Dawadi
    • , Shannon L. Kordus
    • , Abiram Sivanandam
    • , Courtney C. Aldrich
    •  &  Anthony D. Baughn
  • Nature Communications | Article | open

    Broadly neutralizing antibodies targeting HIV Env could potentially be utilized as therapeutics. Here, Steinhardt et al. engineer a trispecific antibody with specificity for the receptor-binding site, a conserved Env glycan patch and the Env membrane proximal region with nearly pan-isolate neutralization breadth and high potency.

    • James J. Steinhardt
    • , Javier Guenaga
    • , Hannah L. Turner
    • , Krisha McKee
    • , Mark K. Louder
    • , Sijy O’Dell
    • , Chi-I Chiang
    • , Lin Lei
    • , Andrey Galkin
    • , Alexander K. Andrianov
    • , Nicole A. Doria-Rose
    • , Robert T. Bailer
    • , Andrew B. Ward
    • , John R. Mascola
    •  &  Yuxing Li

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