Platforms
The chart below depicts ZATA’s versatile platforms forecasting the development of variety of medical products targeting current unmet medical needs.
Oligotherapeutics (ZONs)
Four decades ago, the cofounder of ZATA, Dr. Paul C. Zamecnik, known as the “father of Antisense Therapy”, opened a new chapter in Medicine by showing, together with Mary Stevenson, that oligonucleotides can be used to selectively modulate the expression of target genes (Zamecnik & Stephenson, PNAS, 1978, 75, 280-284). This idea opened endless new possibilities for the treatment of diseases, or for biological research. Yet, the practical realization of these possibilities turned out to be difficult: Natural oligonucleotides do not readily penetrate inside the cells, where there action is, and they have a very short circulation time in vivo, being quickly broken down or excreted by the kidneys. A lot of research has been devoted to the improvement of the properties of natural oligonucleotides through modifications.
The successor of Dr. Zamecnik and current president of ZATA, Dr. David R. Tabatadze, proposed the idea of self-neutralizing oligonucleotides (ZONs) which reduces the problem of low cellular uptake and improves the stability of synthetic oligonucleotides. That idea has been materialized by the intensive work of ZATA’s R&D team and the financial support of the NIH.
The unique innovations behind ZATA’s ZON platform enables such key feature as significantly improved unassisted cellular uptake, improved metabolic stability and circulation time, improved targeting specificity, good solubility, and lack of non-specific aggregation and cytotoxicity. This highly flexible technology is compatible with most of the existing oligonucleotide modifications and can be tailored and optimized for any particular target or type of application (steric block antisense, RNase-H based, siRNA and others), and have the potential to revolutionize the oligotherapy field and expand its application to many new areas.
For closer evaluation of properties and features of ZON platform please click on the link below:
ZATA’s Novel Self-Neutralizing Oligonucleotides with Enhanced Cellular Uptake
Antipathogens
ZATA’s Antipathogenic Compounds (ZAP-Cs)
ZAP-C and ZAP-Systems for pathogens reduction in transfusion blood
Killed Vaccine Candidates
ZAP-Systems
Blood borne pathogens, and especially those that are emerging, re-emerging, or yet unknown can significantly increase the risk of transfusion transmitted diseases. As a result, maintaining the safety of blood transfusions requires constant development and implementation of new blood tests, which, without providing full safety, saps resources and drives up the blood transfusion cost. Presently in the US the number of blood transfusion blood tests exceeds fourteen, without testing for such dangerous pathogens as Zika, Ebola, Malaria, and others. Many low income countries cannot afford the high cost of those tests, and for them transfusion transmitted infections become a major health risk. According to the World Health Organization, as much as 10% of new HIV and malaria infections in developing countries have been acquired through blood transfusion.
To be prepared in advance for emerging pathogens, implementing a comprehensive strategy to inactivate pathogens in transfusion blood is intrinsically more effective than developing tests after emergence. Simple, effective and safe pathogen inactivation in donated blood is a proactive alternative to the current reactionary approach to developing screening tests upon emergence of new blood borne pathogens. Development and implementation of ZATA’s Anti-Pathogen Systems (ZAP-systems) enabling effective reductions of blood borne pathogens addresses that need.
The blood transfusion process and its safety measures are subject to different regulations depending on each country around the globe. The unique versatility of the ZAP-Systems enables the development of four different treatment systems with the minimum modifications that covers all regulatory requirements around the globe without compromising of the safety standards.
Short description of ZAP-C deactivators and ZAP-systems: ZAP-C is a family of small molecules that effectively penetrate the pathogens and selectively and permanently deactivate their genomic molecules, thus eliminating their infectivity, without affecting proteins or other biological components. The cells in the blood intended for transfusion, red blood cells and platelet, are anucleated, i.e. they do not contain nuclei and DNA. Therefore, unlike the pathogens, they are resistant to the effect of the ZAP-C compounds. After inactivation of the blood borne pathogens, the residual ZAP-C is neutralized and the product of neutralization is completely removed by cartridge filtration. The entire process of blood collection, treatment with ZAP-C, inactivation of residual ZAP-C, removal of ZAP-C inactivated product, and final processing of pathogen depleted blood, takes place in a simple, entirely closed, sterile, disposable ZAP-systems.
For further evaluation of properties and feature of ZAP-C and ZAP-Systems please click on the link below:
ZATA’s Closed Systems for Pathogen Reduction in Donated Blood
ZCIs for Killed Vaccines
Killed Whole Pathogen Vaccine Candidates With Preserved Antigenic Epitopes
Among the development of modern vaccines (subunit/conjugate, toxoid, DNA, recombinant, virus-like particles), the traditional live (attenuated) and especially inactivated (killed) vaccines are still overwhelmingly predominant. The presently available deactivating agents (formaldehyde, glutaraldehyde, ß-propiolactone) often modify the pathogen’s proteins. This changes the pathogen’s immunogenicity, which restricts the broad applicability of the method. Vaccination efficacy of currently used killed vaccines is low, less than 60-65%.
Pathogens killed by ZATA’s chemical inactivators (ZCI), demonstrate complete preservation of their antigenic epitopes, which indicates the feasibility of killed vaccines with maximum preservation of antigenic efficacy.
The chemical structure and the mechanism of action of the ZCIs are the same as those ZAP-Cs uses in the transfusion blood purification systems. ZCIs selectively and permanently inactivate pathogens by damaging their genomic molecules without affecting their proteins, and hence their serological characteristics. Differences in size and functionality enables the selection of optimal ZCIs for the inactivation of specific classes or even specific species of pathogens. ZCIs can be used for the development of killed vaccines against viruses, bacteria, and parasites, including pathogens for which no vaccine is currently available.
For further evaluation of the properties and the features of ZCI please click on the link below:
References and IP
Cofounders of ZATA in collaboration of Umass and Harvard Medical Schools co-published over a dozen papers and generated oligonucleotides application IP portfolio. Some of those publications could be seen from the links below.
References:
For David Tabatadze:
Publications: https://www.ncbi.nlm.nih.gov/pubmed/?term=Tabatadze%20D%5BAuthor%5D&cauthor=true&cauthor_uid=21417216
IP: http://www.freepatentsonline.com/result.html?p=1&edit_alert=&srch=xprtsrch&query_txt=David+Tabatadze&uspat=on&usapp=on&pct=on&date_range=all&stemming=on&sort=relevance&search=Search
For Paul Zamecnik:
Publications: https://www.ncbi.nlm.nih.gov/pubmed/?term=Zamecnik%20P%5BAuthor%5D&cauthor=true&cauthor_uid=18699740
Advancing Biomedical Sciences with ZATA 