Precise modifications of complex genomes at the single nucleotide level have been one of the big goals for scientists working in basic and applied genetics,including biotechnology,drug development,gene therapy and synthetic biology.However,the relevant techniques for making these manipulations in model organisms and human cells have been lagging behind the rapid high throughput studies in the post-genomic era with a bottleneck of low efficiency,time consuming and laborious manipulation,and off-targeting problems.Recent discoveries of TALEs(transcription activator-like effectors) coding system and CRISPR(clusters of regularly interspaced short palindromic repeats) immune system in bacteria have enabled the development of customized TALENs(transcription activator-like effector nucleases) and CRISPR/Cas9 to rapidly edit genomic DNA in a variety of cell types,including human cells,and different model organisms at a very high efficiency and specificity.In this review,we first briefly summarize the development and applications of TALENs and CRISPR/Cas9-mediated genome editing technologies;compare the advantages and constraints of each method;particularly,discuss the expected applications of both techniques in the field of site-specific genome modification and stem cell based gene therapy;finally, propose the future directions and perspectives for readers to make the choices.
Body size is one of the features that distinguish one species from another in the biological world. Animals have developed mechanisms to control their body size during normal development. However, how animals cope with genetic alterations and/or environmental stresses to develop into normal-sized adults remain poorly understood. The ability of the animals to develop into a normal-sized adult after the challenges of genetic alterations and/or environmental stresses reveals a robustness of body size control. Here we show that the mutation of dGPAT4, a de novo synthase of lysophosphatidic acid, is a genetic alteration that triggers such a robust response of the animals to body size challenges in Drosophila. Loss of dGPAT4 leads to a severe delay of development, slow growth and resultant small-sized animals during the larval stages, but results in normal-sized adult flies. The robust body size adjustment of the dGPAT4 mutant is likely achieved by corresponding changes in ecdysone and insulin signaling, which is also manifested by compromised food intake. Thus, we propose that a strategy has been evolved by the animals to reach final body size when challenged by genetic alterations, which requires the coordinated ecdysone and insulin signaling.
Yan YanHao WangHanqing ChenAnya Lindstrm-BattleRenjie Jiao
