Synpromics has a portfolio of pre-existing synthetic promoters as well as the unrivalled expertise to design and develop novel promoter candidates according to a specific design brief. We are able to create tissue, or cell-type, selective promoters, and inducible promoters that are controlled by small molecule drugs or biological stimuli.
Synthetic Promoters offer Potential for High Levels of Gene Expression and Specificity
Synthetic promoters are DNA sequences that do not exist in nature but are novel combinations of naturally-occurring transcriptional elements that regulate the activity of a target genes with a high degree of selectivity. Currently, within the industry, naturally occurring promoters are used to drive protein production. Although these natural promoters have evolved for biological functions within a target cell, they are limited as they have not been engineered or optimized for required therapeutic applications.
Synpromics' Promoters are Novel and Patentable
At the core of the technology we are able to design synthetic promoters with the optimal size, selectivity and activity for any given tissue or cell type or mode of delivery. The gene expression profile of the target cell is leveraged to dictate the ultimate synthetic promoter design, and therefore the range of distinct and relevant synthetic promoters that the company can produce is essentially limitless. Importantly, as Synpromics’ promoters are novel DNA sequence combinations and do not exist in nature, each one represents invention rather than discovery and hence can be patented, thus allowing the company to generate an extensive and continually expanding portfolio of commercially valuable patents.
What are DNA Promoters and why are they Important?
Promoters are sequences of DNA that sit beside each gene on the genome and whose function is to activate transcription, the initial process whereby protein is synthesized from the gene template. The promoter recruits a variety of transcription factors to the DNA that interact in a particular fashion so that the gene can be transcribed (see Figure 1 depicting the structure of a promoter).
Figure 1: Structure of a Promoter
Consequently, the resultant mRNA transcript can then be translated into the protein that it encodes. This entire process is fundamental to how gene-based biotech products are designed and developed.
There are a limited number of transcription factors and corresponding cis-regulatory elements contained within a genome and it is how these different factors interact in a myriad of different combinations that dictates which distinct subsets of genes are turned on. This is called a cell’s “gene expression profile” which, for instance, ultimately dictates whether a cell becomes a lung, liver or brain cell.
Synthetic Promoters Designed to Specification
Synpromics has developed technology platform, PromPTTM, incorporating proprietary methodologies used to create libraries of promoter candidates that can be designed and developed according to a discreet set of specifications. These specifications include the size of the promoter, the tissue, cell or multiple cell types that the promoter should be active in and its required strength. Specifications can also include whether the promoter is constitutively expressed in the target cell type(s) or is regulated or inducible in response to a stimulus. These promoters can be designed for both in vivo gene therapy (including replacement therapy or genome editing) or ex vivo gene modified cell therapy applications as well.
In order to do this Synpromics uses a proprietary algorithm to screen the promoter regions of genes that are differentially activated in target cells and then identifies the key cis-regulatory elements responsible for that activity. If a cell is in a diseased state, or infected with a pathogen, or treated with a chemical or biological agent, then the profile of active genes will change. Thus, given that each unique gene expression profile results from the balance of the activities of transcription factors and cis-regulatory elements, it is possible to design synthetic promoters that can be active only under that specific profile. As an example, synthetic promoters can therefore be constructed that are: active only under a particular pathological condition; active in response to infection or treatment; and/or specific to any tissue or cell type.