Biologics | Nature

Article
09 August 2023 | Open Access

TRIM5α restricts poxviruses and is antagonized by CypA and the viral protein C6

The well-characterized HIV restriction factor TRIM5α also restricts orthopoxviruses and is countered by the viral protein C6 and the proviral activity of CypA, which in turn is antagonized by CsA and derivatives alisporivir and NIM811.

Yiqi Zhao
, Yongxu Lu
& Geoffrey L. Smith

Article
28 June 2023 | Open Access

GDF15 promotes weight loss by enhancing energy expenditure in muscle

GDF15 treatment in mice counteracts compensatory reductions in energy expenditure, resulting in greater weight loss and reductions in non-alcoholic fatty liver disease compared to caloric restriction alone.

Dongdong Wang
, Logan K. Townsend
& Gregory R. Steinberg

Perspective | 22 February 2023

CAR immune cells: design principles, resistance and the next generation

This Perspective reviews recent developments in the design and use of chimeric antigen receptors in treatments for cancers and other diseases.

Louai Labanieh
& Crystal L. Mackall

Article
21 September 2022 | Open Access

Antibody targeting of E3 ubiquitin ligases for receptor degradation

Membrane-bound E3 ubiquitin ligases RNF43 and ZNRF3 are overexpressed in colorectal cancer, and can be repurposed using proteolysis-targeting antibodies (PROTABs) to selectively degrade cell-surface receptors in tumours.

Hadir Marei
, Wen-Ting K. Tsai
& Felipe de Sousa e Melo

Article
31 August 2022 | Open Access

Non-viral, specifically targeted CAR-T cells achieve high safety and efficacy in B-NHL

Non-viral CAR-T cells with gene-specific targeted integration are safe and effective in patients with lymphoma.

Jiqin Zhang
, Yongxian Hu
& He Huang

Article | 24 November 2021

Structural basis for ligand reception by anaplastic lymphoma kinase

Analysis of crystal structures of anaplastic lymphoma kinase elucidate the mechanism by which ligand binding and the glycine-rich domain regulate its activity.

Tongqing Li
, Steven E. Stayrook
& Daryl E. Klein

Article | 03 June 2021

Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants

An engineered IgM antibody administered intranasally in mice shows high prophylactic efficacy and therapeutic efficacy against SARS-CoV-2, and is also effective against multiple variants of concern that are resistant to IgG-based therapeutics.

Zhiqiang Ku
, Xuping Xie
& Zhiqiang An

Article | 25 March 2021

Bispecific IgG neutralizes SARS-CoV-2 variants and prevents escape in mice

The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape.

Raoul De Gasparo
, Mattia Pedotti
& Luca Varani

Article | 21 October 2020

Cas9 gene therapy for Angelman syndrome traps Ube3a-ATS long non-coding RNA

Genomic integration of an adeno-associated virus vector in a mouse model of Angelman syndrome unsilences paternal Ube3a and rescues anatomical and behavioural phenotypes, suggesting a pathway towards the treatment of this neurodevelopmental disorder.

Justin M. Wolter
, Hanqian Mao
& Mark J. Zylka

Article | 08 October 2020

Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection

An antibody Fc domain variant with enhanced binding to an activating Fc receptor on dendritic cells promotes the induction of a protective CD8 T cell response.

Stylianos Bournazos
, Davide Corti
& Jeffrey V. Ravetch

Article | 29 July 2020

An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma

Results of an exploratory interim analysis from a phase I trial show that an RNA vaccine targeted towards four melanoma-associated antigens produces durable objective responses in patients with melanoma that are accompanied by strong CD4⁺ and CD8⁺ T-cell immunity.

Ugur Sahin
, Petra Oehm
& Özlem Türeci

Article | 01 July 2020

Suppression of proteolipid protein rescues Pelizaeus–Merzbacher disease

In a mouse model of the leukodystrophy Pelizaeus–Merzbacher disease, myelination, motor performance, respiratory function and lifespan are improved by suppressing proteolipid protein expression, suggesting PLP1 as a therapeutic target for human patients with this disease and, more broadly, antisense oligonucleotides as a pharmaceutical modality for treatment of myelin disorders.

Matthew S. Elitt
, Lilianne Barbar
& Paul J. Tesar

Article | 24 June 2020

IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy

An engineered version of IL-18 that is resistant to binding by the soluble decoy receptor IL-18BP shows strong anti-tumour activity in mouse models of cancer.

Ting Zhou
, William Damsky
& Aaron M. Ring

Article | 18 May 2020

Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody

The monoclonal antibody S309, identified from memory B cells of an individual infected with SARS-CoV in 2003, or antibody cocktails that contain this antibody potently neutralize SARS-CoV-2.

Dora Pinto
, Young-Jun Park
& Davide Corti

Article | 25 September 2019

Treatment of type 2 diabetes with the designer cytokine IC7Fc

The chimeric cytokine IC7Fc combines the beneficial effects of the cytokines IL-6 and CNTF on weight loss and metabolism in mice, with no obvious side effects in mice and non-human primates.

Maria Findeisen
, Tamara L. Allen
& Mark A. Febbraio

Article | 05 September 2018

Coupling of bone resorption and formation by RANKL reverse signalling

Osteoclasts secrete small extracellular vesicles that stimulate osteoblasts, promoting bone formation via receptor activator of nuclear factor-kappa B ligand (RANKL), thereby linking bone formation and resorption.

Yuki Ikebuchi
, Shigeki Aoki
& Hiroshi Suzuki

Article | 19 December 2012

Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants

Nuclear genome transfer using unfertilized donor oocytes is performed and shown to be effective in preventing the transmission of mitochondrial DNA mutations; the swapped oocytes can develop to the blastocyst stage, and produce parthenogenetic embryonic stem-cell lines that show normal karyotypes and only mitochondrial DNA from the donor oocyte.

Daniel Paull
, Valentina Emmanuele
& Dieter Egli

Article | 05 December 2012

Functional screening identifies miRNAs inducing cardiac regeneration

The human heart regenerates poorly, causing insufficient healing after injury; here, microRNAs screened for the ability to induce cardiomyocyte proliferation are shown to stimulate cardiac regeneration and almost complete recovery of the heart after infarction.

Ana Eulalio
, Miguel Mano
& Mauro Giacca

Letter | 10 October 2012

Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation

A genetically engineered mouse model is used to determine the mechanism of acquired resistance to adoptive therapy with cytotoxic T cells specific for a melanocytic differentiation antigen; tumour necrosis factor (TNF)-α is identified as a crucial factor that causes reversible dedifferentiation of mouse and human melanoma cells.

Jennifer Landsberg
, Judith Kohlmeyer
& Thomas Tüting

News | 07 August 2012

Stem-cell pioneer banks on future therapies

Japanese researcher plans cache of induced stem cells to supply clinical trials.

David Cyranoski

News & Views | 01 August 2012

Kill the messenger where it lives

A mutant repeating DNA sequence produces a toxic RNA molecule that causes the neuromuscular disorder myotonic dystrophy type 1. An ‘antisense’ therapy that targets this RNA in cell nuclei shows promise in mice. See Letter p.111

Peter K. Todd
& Henry L. Paulson

Letter | 01 August 2012

Targeting nuclear RNA for in vivo correction of myotonic dystrophy

Nuclear-retained transcripts containing expanded repeats are shown to be sensitive to antisense silencing, and in a transgenic mouse model of myotonic dystrophy type 1, systemic administration of ASOs causes a rapid knockdown of the toxic RNA in skeletal muscle, correcting some hallmark features of the disease.

Thurman M. Wheeler
, Andrew J. Leger
& Charles A. Thornton

News | 27 July 2012

FDA’s claims over stem cells upheld

Drug watchdog wins right to regulate controversial therapies.

David Cyranoski

News Explainer | 20 July 2012

The great gene-patent debate

How the Myriad Genetics gene-patent case might affect personalized medicine.

Amy Maxmen

News | 20 July 2012

Europe nears first approval for gene therapy

Treatment for rare fat-processing disease gains approval from medicines regulator.

Daniel Cressey

Research Highlights | 04 July 2012

Gene blocks effects of stress

Research Highlights | 04 July 2012

Silencing Huntington's gene

Correspondence | 30 May 2012

Personalized drugs should cut care costs

Nafees N. Malik

News | 08 May 2012

Drug-making plant blooms

Approval of a ‘biologic’ manufactured in plant cells may pave the way for similar products.

Amy Maxmen

Research Highlights | 01 February 2012

An eye for gene repair

Letter | 29 January 2012

G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody

Determination of the crystal structure of the human A_2A adenosine receptor in complex with an inverse-agonist antibody shows that the allosteric site of the receptor inhibits agonist binding and that the antibody locks the receptor in an inactive conformation.

Tomoya Hino
, Takatoshi Arakawa
& Takeshi Murata

News Feature | 11 January 2012

Stem-cell research: Never say die

With a history of public blunders, can Advanced Cell Technology make embryonic stem-cell therapies a reality?

Corie Lok

Outlook | 21 December 2011

Biodiversity: Endangered and in demand

With an ingredients list that includes rhino horn and tiger bone, traditional Asian medicine is on a collision course with wildlife preservation.

Duncan Graham-Rowe

Outlook | 21 December 2011

Perspective: All systems go

Systems science can provide guidance in capturing the complementary approaches to healthcare, says Jan van der Greef.

Jan van der Greef

Outlook | 21 December 2011

Modernization: One step at a time

The repertoire of traditional Chinese medicine could offer rich pickings for modern drug developers, but researchers must first define and test herbal concoctions.