Volume 16 Issue 9, September 2015

Genome engineering can be used to introduce targeted genetic changes to design and reprogramme organisms, to introduce new functionalities and to discover causal associations in evolving phenotypes. In this Review, the rationale, techniques and applications in genome engineering are described, outlining key advances, technological goals and challenges, as genome engineering approaches move towards massively parallel platforms.

There is accumulating evidence that the genetic code is not fixed but instead varies across organisms and that decoding is influenced by genomic and physiological contexts. This Review describes the various types of non-standard decoding, including altered codon meanings and ribosomal frameshifting, and highlights their pervasiveness, classification and biological implications.

Mitochondrial DNA (mtDNA) mutations have been associated with numerous human diseases, from severe inherited disorders to common late-onset diseases. In this Review, the authors consider the origins of these mtDNA mutations in a single cell, their spread across populations and their contributions to disease risk.

Small interfering RNA (siRNA)-based drugs offer a promising approach to block the synthesis of disease-causing proteins, although their delivery has posed challenges. The authors review recent advances in siRNA therapeutics, including progress in overcoming delivery challenges, and clinical trials showing efficient and durable gene knockdown in the liver.

The authors provide a comprehensive survey of international legislation and policies guiding the return of whole-genome-sequencing-based genetic testing results to patients or study participants, within the context of both clinical and research settings.