GeneOptimizer: Accelerating Discovery

Protein therapies have tremendous potential to treat cancer, infectious diseases, neurodegenerative conditions, and much more, however producing the most effective recombinant antibodies and other proteins can be a slow and costly journey.

Optimizing proteins is an iterative process in which researchers design, test and redesign genetic material to give therapeutic molecules the most advantageous traits. Labs want to quickly learn whether the gene that has been designed will produce the proteins they need. This work is often slow and tedious, causing a hurdle to drug discovery.

While custom gene synthesis allows labs to precisely design DNA to their needs, it doesn’t fully solve the problem. Researchers must design their synthetic genes to maximize RNA and protein expression.

Thermo Fisher Scientific’s GeneOptimizer algorithm is a useful tool to help with this problem. This sophisticated software accelerates labs’ ability to design the right genes to produce the desired protein yield in the chosen expression system. This improved efficiency can accelerate early discovery and shorten the timeline between concept and proof.
 

The GeneOptimizer algorithm is easily accessible for custom gene synthesis on Thermo Fisher Scientific’s GeneArt Services Dashboard or as part of a complete gene-to-protein project. Researchers can design their ideal synthetic gene by uploading their sequence, selecting the expression system, and specifying the cloning vector and other sequence details, such as open reading frames, untranslated regions, and cloning sites.

Once the information is submitted, GeneOptimizer software generates the best DNA sequence based on many relevant parameters.

Efficient gene optimization accelerates discovery research by reducing the risk of designing poorly performing DNA sequences that produce inadequate protein yields. This gives leadership the necessary information to make important business decisions. Most importantly, it holds the potential to quicken the drug discovery process.
 

One of GeneOptimizer’s most important features is codon optimization. Since multiple codons can translate into a single amino acid, the DNA sequence can be adjusted without changing the protein sequence. This is critically important for optimal protein expression since codon preference differs by organism. GeneOptimizer customizes codon selection to each unique expression system—whether it is mammalian, insect, or other popular options—helping labs create the best combinations to increase protein yields.

Gene optimization to improve protein expression requires much more than codon optimization. Labs must also guard against cryptic splicing and other mechanisms that can impair mRNA and ultimately protein production.

GeneOptimizer was developed to address over 20 different parameters linked to efficient (or inefficient) gene expression, including transcription, splicing, translation, and mRNA degradation. The algorithm crunches these and other parameters to produce the ideal DNA sequence for that system. As a result, the construct is designed from the beginning to express the target protein as efficiently as possible.

In addition to using GeneOptimizer to design a target gene’s coding sequence for maximum protein expression, Thermo Fisher Scientific’s gene synthesis services support efforts to efficiently design surrounding, noncoding DNA. High foreign protein expression levels (driven by a strong promoter) or insufficient termination (driven by a weak terminator) can also inhibit protein yields. To balance these factors, custom genes produced by GeneArt Gene Synthesis can be delivered in a variety of different Invitrogen vectors or in a unique vector provided by the researcher.
 

When developing the right expression construct, speed is always a vital consideration, as companies must show ongoing progress for investors and other stakeholders. This process can be accelerated significantly with transient expression pilots.

Stable cell lines can take weeks or months to develop. If that cell line fails to produce the most advantageous protein, the process must start again from the beginning.

Transient expression of candidate proteins offers the tremendous advantage of accelerating speed to decision. Rather than taking weeks to determine whether a gene construct is effective, each of these iterations can be accomplished much faster and in parallel. This approach allows labs to compare the traits in different constructs rapidly.

Once the lab has identified the most productive and therapeutically advantageous gene sequence, they can move on to create a stable cell line, which can be used repeatedly. Thermo Fisher Scientific’s GeneArt Protein Expression and Purification Services are a ready partner to help labs optimize gene expression and speed discovery. By shortening the pipeline, these capabilities can help make a greater impact on patient care.