Horizontal Gene Transfer
The phenomenon of horizontal genomic transfer enables organisms to avoid infections and become resistant to toxins. Previously thought to only be present in species like bacteria and fungi, Kodikaz has discovered horizontal genomic transfer in humans. Horizontal gene transfer in human cancerous cells has the potential to revolutionize disease management in oncology and potentially many other diseases.
Kodikaz has not only discovered horizontal gene transfer in humans but has decoded the mechanism by which it is targeted to discreet cells and has leveraged this knowledge to create cell specific “Zip-Codes”. These “Zip-Codes” can be utilized to target and deliver therapeutic payloads that hit only the cell of interest and not other cells or organs in the body.
While completely new biology with much to learn and explore, this new Zip-Code technology is a dramatic scientific breakthrough which we are confident will lead to tremendous new health solutions in the future.
Our Product Platform
Transposon Receptor Gene Transfer (TaRGeT Zip-Codes)™
Our Transposon Receptor Gene Transfer Zip- Codes (TaRGeT Zip-Codes)™, are cell-specific and can be used in gene delivery applications, without the challenges of viral approaches.
TaRGeT Zip-Codes™ are constructs of synthetic DNA that have tropism to discreet cell types and can be modularly linked with a diversity of therapeutic payloads. Kodikaz is developing a library of Zip-Codes to attack each cancerous cell of interest. The TaRGeT Zip-Codes™ are able to be manufactured at large scale and in a cost effective manner.
How TaRGeT Zip-Codes™ Work
1. Engineered TaRGeT Zip-Code™ with Payload
TaRGeT Zip-Codes™ are sequences of 300-500bp in length that are synthetically manufactured and depending on the therapy chosen are linked with promoters and guide sequences along with trans-genes. This manufacturing process is both scalable and provides for a product that is highly characterized and uniform. The product offers a diversity of therapeutic payloads to be employed such as RNAi, cytotoxic agents, lethal genes, gene editing platforms (e.g. CRISPR Cas-9) as well as proteins/antibodies.
2. Contact with Cell of Specific Interest
The TaRGeT Zip-Code™ products are placed into solution, systemically administered and circulate until they come into contact with specific cancer cells of interests.
3. Recognition and Endocytosis
Once in contact with the targeted cancer cell the Zip-Code is recognized by cell receptors and the entire payload and Zip-Code product is endocytosed into the nucleus of the cell. The Zip-Codes have protective attributes that enable them to bypass TLR and other known cell immune rejection mechanisms.
4. Gene Transfer and Modified Cell
Once inside the nucleus the payload is “unpackaged” and the Zip-Code integration sequence permits the incorporation of the trans gene into the genome of the host cell.
Engineered Synthetic Zip-Codes(tm)
- No bacteria or viruses required
- No elicited immune responses (permits redosing)
- Natural integration into the target cell genome
- Universally specific for target cells not patient specific
(Recognition and gene transfer)
- Hits the target cell exclusively
- Incorporates into genome
- On/Off Switch controls process
Payload Size (>20kb)
- Capable of delivering large payloads >20kb in size
Do Zip-Codes integrate or localize in other organs, such as the brain or liver?
The TaRGeT Zip-Codes™ have thus far been proven to not localize or be sequestered into other organs. In early in-vivo studies Zip-Codes have demonstrated no detectable levels in the brain, kidney, liver, lung, spleen or pancreas. We believe that this level of specificity enables lower therapeutic dose requirements and ultimately a much safer product.
Are there Zip-Codes for both cell specific honing and integration?
The Zip-Codes are a complex sequence that contain both the cell specific and integration aspects. Though both might not always be required the Zip-Codes contain both attributes.
Are normal cells targeted and effected by Zip-Codes?
In current studies we have not shown that the Zip-Codes have any significant effect on normal cells. We will continue to study this technology to demonstrate if Zip-Codes are cable of transfecting normal cells.
What is the relative size of Zip-Codes?
TaRGeT Zip-Codes™ are typically 300-500 bp in length and are different for every cell type. As we continue to interrogate the technology we expect to have variation in sizes of the ultimate products.
Are the Zip-Codes stable in solution and in-vivo when systemically delivered?
We have demonstrated that these Zip-Codes are stable for long periods of time. There are a variety of reasons why they are not degraded and the include lower levels of DNAse activity in cancer patients, the size and structure of the Zip-Codes and other biological protective mechanisms.