PRINCIPAL R&D PROGRAMS

Early Detection of Disease from Blood Proteomic Signatures

The Need: It is universally recognized that early detection of cancer and coronary artery disease leads to dramatically improved health outcomes. Yet, there is great scarcity of minimally invasive, economically feasible approaches to early detection. The ability to obtain early warning information from proteins and other molecules in blood or other biological fluids would represent an epochal advance. However, this approach is extraordinarily difficult, since many proteins need to be analyzed at the same time,  the molecular population present in the blood is extremely diverse, and the fact that the proteins of interest are billion-fold less abundant that the most concentrated proteins.  This poses the ultimate ‘needle-in-the-haystack’ problem.

Our Approach: We have invented and are developing nanotechnology-based chips and particles (proteomic nanochips) that can sort out and concentrate proteins of interest from blood samples. The chips and particles are interrogated with Mass Spectrometry, with no need for additional sample preparation steps, leading to the potential for very high-throughput.

State of Development: We have demonstrated the proteomic nanochip technology in the context of the detection and monitoring of the development of breast cancer in laboratory animals. We have published several papers establishing the ability of our system to: reach unprecedented limits-of-detection (very low concentrations); effectively sort out and enrich the desired part of the molecular spectrum (low molecular weight proteome). With this approach, we were the first to identify a new circulatory protein (VEGF-117) that is believed to have extraordinary importance in the angiogenesis (new blood vessel formation) that is required for cancer growth. 

Injectable NanoVectors for Directed (Targeted/Personalized) Therapeutics

The Need:  Despite extraordinary progress in the laboratory, cancer mortality has not been reduced by any significant amount in the last fifty years. The main reasons are that ‘cancer’ is actually several hundreds of disease, which differ dramatically in terms of their biology, and respond very differently to drugs. Like malignant snow-flakes, no two cancers are identical, if one looks closely enough. Furthermore, very different metastatic colonies will evolve from the same primary cancer in a patient, leading to the impossibility of treatment with a single combination of drugs. Finally, upstream from the problem of successful recognition of molecular targets for therapeutic agents is the need to achieve the right distribution of drugs: the same drug in different individuals will disperse in their body in different way, because of intrinsic differences in the biology of the individual and their disease. This happens because the body contains numerous ‘traps’ (biobarriers) that severaly limit the penetration substances such as drugs into the body. The quadruple problem of identifying different molecular targets, avoiding all biobarriers, delivering one or more cancer cell killing modes, and personalizing therapy has historically been addressed by trying to endow individual drug molecules with all of these capabilities. This strategy has met with limited success.      

Our Approach: We believe that nanotech offers unprecedented opportunities to develop treatments that increase therapeutic efficacy, decrease undesired side effects, and effectively achieve the personalization of intervention. The fundamentally novel approach is the decoupling of the quadruple functions through the use of ‘carrier’ particles (“NanoVectors”) that possess sufficient multi-functionality to avoid biological barriers and recognize their targets. Their payload comprises simple cell killing agents (FDA-approved, possibly generic drugs), which are released at the desired site of intervention. In our laboratories we employ multi-stage NanoVectors to reach these objectives.

State of Development: We have developed the fundamental multi-stage NanoVector technology, and are in the process of validating it in-vitro and in animal models. We have developed the mathematical tools for the Rational Design and selection from a combinatorial NanoVector library of the proper NanoVector therapy for individual conditions.

Intelligent Implants for Controlled Time Release of Therapy

The Need:  The release of drugs from implants for a sustained period of time offers substantial advantages for the treatment of many pathologies. The potential advantages include improve therapeutic efficacy, the reduction of undesired side effects, patient convenience, patient compliance, and treatment cost reductions. While several problems in sustained, long-term release of drugs have been solved, leading to successful commercial clinical products, suitable release systems for many biotechnological drugs have not been developed yet. Thus, ample opportunities exist for entering the drug delivery marketplace. Furthermore, no implant has been developed or commercialized yet, that has the ability to do more than simply releasing a drug at a constant rate. Additional medically desirable features of such an implant would include the ability to control the release rate by preprogramming, activation from remote controls, and self-regulated release in response to varying conditions in the body, at the implant location.     

Our Approach: We have developed and validated multiple generations of controlled-release implants, based on our proprietary nano-channel technology. In brief: We employ our proprietary methods to make silicon-based chips that present with a multitude of nano-scale channels. Tailoring the channel size and chemistry to the molecules of interest it is possible to attain the desired constant release profiles, for period of several months, even for biotechnological drugs. Furthermore, we have shown that applying a very small electrical field across the channel gives the ability to actively control the release rates. This offers the opportunity to develop smart pre-programmed, remotely activated, and self-regulated delivery implants.