RNA therapies

With more than a dozen RNA therapies being tested in clinical trials, patients with many previously untreatable conditions have cause for optimism.

Treatments that target RNA or deliver it to cells fall into three broad categories, with hybrid approaches also emerging.

After a groundswell of hype and a sceptical backlash, the pharmaceutical industry is learning how to leverage RNA interference in the clinic.

Carlos Heras-Palou explains his part in making the first RNA-interference therapeutic available to people with rare diseases.

Delivery difficulties brought the nascent research field to its knees, but approval of the first RNA interference drug offers hope.

The technology could help to boost immunity against cancer, influenza and much more.

Researchers hope that understanding the many roles of non-coding RNA in heart health and cardiovascular disease could deliver a therapeutic breakthrough.

As a source of potential treatments, gene editing gets all the attention. That needs to change, argues Lorna Harries.

When two pharmaceutical companies turned their attention to a rare condition, they came up with different strategies for targeting RNA. Now, RNA therapies for other hereditary conditions are within the sights of the industry.

A decrease in ataxin-2 levels leads to a reduction in the aggregation of TDP-43, markedly increased lifespan and improved motor function in a transgenic mouse model of TDP-43 proteinopathy.

Antisense oligonucleotides against ATXN2 improved motor neuron function and restored firing frequency in cerebellar Purkinje cells in mouse models of spinocerebellar ataxia type 2.

As the clinical potential of RNA therapeutics begins to be unveiled, expanding the range of tissue types that can be targeted for delivery of these drugs is now the main hurdle to overcome.

An siRNA targeting antithrombin promotes hemostasis in mouse and nonhuman primate models of hemophilia and could represent a new therapeutic option for this disease.

Recent progress in delivering RNA therapeutics to the inside of cells might lead to more success in clinical applications.

The therapeutic potential ofin vitro-transcribed mRNA (IVT mRNA) extends from prophylactic and therapeutic vaccines to applications such as protein replacement and genome engineering. In this Review, the authors describe the recent developments in the IVT mRNA field, discuss the class-specific challenges with regards to translating IVT mRNA into a biopharmaceutical, and provide an overview of IVT mRNA drugs in development for different indications.

In this Review, Pastoret al. provide an overview of RNA-based agents used in cancer immunotherapy — ranging from RNA vaccines encoding cancer neoantigens to interference RNAs and protein-binding RNA aptamers — providing insights into this emerging field.

RNA antisense oligonucleotide therapy to restore normal splicing of a ciliopathy gene shows promising safety and efficacy results in a clinical trial to treat a form of childhood blindness.

Systemic administration of human PBGD mRNA encapsulated in lipid nanoparticles ameliorates disease phenotypes in mouse and rabbit models of acute hepatic porphyria and is safe in nonhuman primates.