Gene therapy has historically been defined as the addition of new genes to human cells. However, the recent advent of genome-editing technologies has enabled a new paradigm in which the sequence of the human genome can be precisely manipulated to achieve a therapeutic effect. This includes the correction of mutations that cause disease, the addition of therapeutic genes to specific sites in the...

The complex gene expression mechanisms that occur in plant mitochondria, such as RNA editing and splicing, are not yet well understood. RNA editing in higher plant mitochondria is a highly specific process which modifies mRNA sequences by C-to-U conversions. It has been suggested that in some cases this process is required for splicing. Here, we use an experimental model based on the introducti...

RNA editing is a posttranscriptional modification that can lead to a change in the encoded protein sequence of a gene. Although a few cases of mammalian coding RNA editing are known to be functionally important, the vast majority of over 2,000 A-to-I editing sites that have been identified from the coding regions of the human genome are likely nonadaptive, representing tolerable promiscuous tar...

Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematological diseases. However, the limited efficiency of homology-directed editing in primitive HSPCs constrains the yield of corrected cells and might affect the feasibility and safety of clinical translation. These concerns need to be addressed in stringent preclinical models ...

RNA editing usually affects only a fraction of expressed transcripts and there is a vast amount of variation in editing levels of ADAR (adenosine deaminase, RNA-specific) targets. Here we explore natural genetic variation affecting editing levels of particular sites in 81 natural strains of Drosophila melanogaster. The analysis of associations between editing levels and single-nucleotide polymo...

Editing of the pre-mRNA for the serotonin receptor 2C (5-HT2CR) by site-specific adenosine deamination (A-to-I pre-mRNA editing) substantially increases the functional plasticity of this key neurotransmitter receptor and is thought to contribute to homeostatic mechanisms in neurons. 5-HT2CR mRNA editing generates up to 24 different receptor isoforms. The extent of editing correlates with 5-HT2C...

Antibody diversity is generated through the random recombination of immunoglobulin gene segments. As a consequence of this stochastic process, antibodies recognizing self-antigens can also be produced. Continued antibody gene rearrangement, termed receptor editing, is an important mechanism of central B cell tolerance that serves to alter the antibody specificity of developing B cells. Although...

Just a few years ago, molecular biologists hoping to alter the genome of their favorite organisms faced an arduous task and likely weeks of genetic tinkering. Today, those scientists can quickly destroy or edit a gene with a new technology called CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9. “It really opens up the genome of virtually every organism that’s been sequenc...