What is DNE?


Precision BioSciences' Directed Nuclease Editor (DNE) is a robust platform for genome engineering. The technology is based on the production of custom-made DNA-cutting enzymes called "DNE meganucleases". Using state-of-the-art protein engineering techniques, Precision BioSciences alters the genetic sequence of a natural genome-editing meganuclease to create a custom meganuclease with unique DNA-recognition and cleavage properties. The result is a DNE enzyme with the ability to precisely modify a specific, user-defined target within a genome. The targeted manipulation of genomic DNA has a broad range of applications including the correction of genetic disorders, the treatment of viral infections, the improvement of crops, and the engineering of cell lines for research or biomanufacturing. DNE is a proven technology with numerous successful applications in mammalian and plant cells.


A unique tool for genomic molecular biology.
Endonucleases are proteins that cut double stranded DNA. The most widely used endonucleases are restriction enzymes which recognize and cut 4 - 8 base pair (bp) sites. Since their discovery in the 1970's, restriction enzymes have revolutionized the field of molecular biology by allowing the manipulation of short DNA sequences. Due to their relatively small recognition sites, however, conventional restriction enzymes are not suitable for the manipulation of large DNA sequences such as whole genomes. For example, a 6 bp recognition site will occur randomly once in 46 or 4096 bp, so an average restriction enzyme will cut nearly 1.5 million times within the 6 billion base pair genome of humans.


Another class of endonucleases, referred to as "meganucleases" or "homing endonucleases" recognize much larger DNA sequences (14 - 40 bp) and, hence, are frequently able to recognize a single site within a large genome. Most of the enzymes in this family are carried in selfish introns and inteins, which use the meganuclease to precisely target their insertion into actively transcribed genes in a process known as "homing". Because these natural meganucleases are evolved for function in living cells with large genomes, they must exhibit exquisite levels of sequence specificity to ensure that only a single "address" within the genome is cut and modified. While this unusual level of specificity is key to the genome editing power of meganucleases, it has also greatly limited the contribution of natural meganucleases to biotechnology. This is because the likelihood of finding a recognition site for a natural meganuclease at a genomic locus of interest to the biotechnology community is exceedingly small.


Precision BioSciences has developed a new class of custom engineered endonucleases that recognize and cut novel DNA sites while maintaining the exquisite sequence specificity of meganucleases. This allows us to redirect meganuclease-based genome-editing systems to new locations in virtually any cell type. The result is DNE technology, giving scientists the ability to systematically manipulate the chromosomal DNA sequence of a cell. Just as restriction enzymes revolutionized the field of molecular biology, DNE is ushering in the era of "genomic molecular biology" and is already creating value across multiple facets of biotechnology.


Technology Innovation
of the Year

‘Frost & Sullivan names Precision BioSciences’ Directed Nuclease Editor the Genomics Technology Innovation of the Year’

Read More