TAL effector science

"This appears to be the first demonstration that TALENs can produce heritable mutations in a vertebrate organism. Based on our results, it is plausible that this technology could be applied to other model organisms, especially those in which gene-targeting methods are still lacking or very preliminary."

"Compared with zinc-finger proteins4, 5, TAL effectors permit more predictable and specific binding to target DNA6, and therefore allow researchers to engineer genomes precisely without the need for laborious screening to identify a DNA binding domain with the requisite specificity."

"The NK RVD has been reported to bind to G more specifically than NN does"

"Survival rates were similar for embryos injected with mRNAs encoding either NN- or NK-containing TALENs (Fig. 1b). However, the NN embryos exhibited a noticeably higher mutation rate than the NK embryos"

(Image: http://ec.europa.eu/research/health/genomics/newsletter/issue2/newprojects_en.htm)

Two papers published today, one in Nature Biotechnology and one in Nature Methods, show that although zinc-finger nucleases are highly specific, the methods previously used to predict where they might go wrong miss the mark.

Good to have an alternative strategy...

Given that the frequencies of mutation and the extent of toxicities we observe are similar to what we have seen with ZFNs, we expect that TALEN-induced mutations should be efficiently passed through the germ line.

all six TALEN monomers we constructed showed high mutagenesis activities when tested in various pairwise combinations. This suggests that the TALEN framework is also highly robust and effective in zebrafish.

TALENs we made in zebrafish did not show toxicity substantially different from that observed with expression of ZFNs

TALENs may offer potential advantages over ZFNs for mutagenesis of genes in zebrafish and other model organisms such as Caenorhabditis elegans12, because they can be easily and quickly assembled in a modular fashion and can potentially target a greater range of DNA sequences. Thus, we expect that the ability to use both ZFNs and TALENs should enable any researcher to rapidly and easily create targeted mutations in any zebrafish gene of interest.

(Picture from: http://www.digs-bb.de)