A new tool for genome editing

Bacteria defense system takes its place in human genome editing

        An RNA based nuclear acids degradation system found in bacteria and archaea was tamed for human genome editing.

        Genomes store information of life and human genome editing holds promise to improve human’ health and overcome diseases. Some available genome editing tools attract wide interests. Zinc finger nuclease (ZFN) technology and Transcription activator-like effector nucleases (TALENs), both of which were invented recently for genome editing, won the Method of the Year 2011, awarded by the journal Nature Methods. Lately, a new genome editing tool was released in Science¹.

        This new technology is based on an exogenous nuclear acid degradation system in bacteria and archaea. During evolution, bacteria and archaea face frequent and tremendous threats from environment. Exogenous nuclear acid constitute a main jeopardy because genomes of bacteria and archaea are not protected as well as that of advanced life. Bacteria and archaea thus develop a mechanism to combat exogenous nuclear acid. This system adopts RNA, which is characteristic of short repeats, and proteins to degrade invading nuclear acid. Shorted and repeated RNA is mainly responsible for the recognition of threatening exogenous nuclear acids whereas the RNA associated protein takes care of the degradation step. Although this nuclear acid degradation aims at invading DNA or RNA, they may be modified to target the human genome.

        Scientists in Havard Medical School engineer this nuclear acids degradation system in order to obtain targeted degradation of DNA sequence in human genome. The designed DNA sequence targeting interested DNA in human genome was linked to a DNA scaffold that facilitates the access of the protein responsible for degradation. The protein for degradation was also engineered to ensure location and high expression in human cells. The artificial DNA and protein are sent to human cells together. The designed DNA will recognize its corresponding DNA in the genome. Then the protein will function to cut the DNA in the genome. All mentioned above is what this bacteria originated system does. Other steps were finished by DNA repair system in human cells. Realizing a DNA damage (here it is broken DNA), the DNA repair system will try to repair it based on a similar DNA sequence, which is the special designed DNA in the artificial DNA donor in this case. The desired mutations, insertions, deletions will be thus possible.

        What are the advantages of this new genome editing tool compared to other tools? This system is easier and more efficient compared to ZFNs and TALENs. Both ZFNs and TALENs adopt specific proteins to recognize interested DNA sequence. It is tricky to design appropriate protein scaffold to match DNA in genome. The bacteria originated gene editing system uses DNA to recognize DNA in genome so it is easier to design DNA sequence. Actually, the authors have designed DNA sequences that able to cover about 40.5% exons in human genome. This bacteria originated DNA editing tool is also effective. In the Science paper, this new gene editing system achieved at most about 8% gene editing rate whereas TALENs resulted in not more than 1% gene editing rate.  

        A key standard to evaluate a gene editing tool is its specificity. That means it will favor interested genome regions but not other regions. Theoretically, this bacterial originated DNA editing system is specific because it usually uses 20 nucleotides, the length of which guarantees the required specificity in human genome, to recognize genome DNA. However, off-target effect of genome editing is still necessary. The Science paper did not resolve this concern.

        An exciting thing about this bacteria originated gene editing tool is there is more space to develop this technology. Both DNA scaffold and degradation proteins can be engineered to improve their efficacy and specificity.