The ErrASE Synthetic Gene Error Correction kit from Novici

In December Novici Biotech started shipping a true error correction system for gene synthesis.  Novici uses the ErrASE system in house to assemble multi-kB genes from unpurified 60-mers.  This dramatically reduces costs, as anyone familiar with purchasing oligos will appreciate.  I can report that in one step the kit provides error correction equal to what one of the "big four" gene synthesis houses does via error removal.  One application of the kit reduces errors due to insertions, deletions, and substitutions by a factor of 20 or so.  I am waiting to hear what happens with two applications.  Using ErrASE essentially just involves a short incubation step.  The kit is designed to be compatible with existing manual and automated work flows.  (Full disclosure: Novici is a client of Biodesic.)

Synthetic genes are almost always assembled using single-stranded DNA, and those oligos tend to contain sequence errors.  Purification of the source oligos can improve the purity of the pool, but at the cost of throwing away ~90% of the oligos.  After assembly, the usual remedy for errors is to remove the genes that contain mistakes (for example using MutS, as I wrote about several years ago) and then sequence a number of the remaining clones to find one that has the correct sequence.

I mentioned ErrASE briefly in my commentary in Nature Biotechnology in December on "The changing economics of DNA synthesis".  It is the sort of advance that should facilitate gene assembly at ever lower costs, both because it reduces input costs through using unpurified oligos and because it reduces sequencing costs on the back end.  The combination of inexpensive oligos and ErrASE should enable DIYers to assemble synthetic genes and genetic circuits on the benchtop if they don't want to pay for the service.