||Gene Regulation Technology
All living things are composed of cells that have a predetermined lifespan; once a cell has outlived its usefulness, it is triggered to die to ensure the overall health of the organism. However, cells may die prematurely or evade this control mechanism, throwing this equilibrium out of balance, often causing disease or death of the organism. Continue reading
In humans, programmed cell death is known as apoptosis. Premature cell death is symptomatic of many ischemic and inflammatory conditions. Cancerous cells behave in the opposite manner. One of the traits common to many cancers is the presence of cells that do not undergo apoptosis.
In plants, factors such as drought, temperature and disease can accelerate cell death, which is termed senescence. This leads to rotten fruit, smaller plants and wilted flowers, amongst other undesirable effects. Despite the different terminology, the processes and genes involved in cell death are virtually identical in plants and humans.
We have characterized an important suite of genes that regulate senescence and apoptosis, which are the basis of Senesco’s gene regulation technology. Our research and development have shown that we can precisely target these genes for both agricultural and human health applications. Our technology is based on the regulation of these existing genes, not the addition of foreign genes.
We have developed and constructed the world’s first “spatially addressed” antibody library. Using advanced synthetic biology, high throughput parallel protein production, and bioinformatics, Senesco has created an expansive combinatorial collection of recombinant IgGs in microtiter plates where each well contains an antibody of known concentration, composition, and sequence. In contrast to immunization and display methods, the Senesco “spatially addressed” library allows rapid cell-based evaluation of each individual member, in a manner analogous to traditional small molecule drug discovery approaches. Thus, drug activity can be identified as opposed to simply target binding. Multiple preclinical antibodies have been discovered and are in various stages of preclinical development.
Human IgG scaffolds have been merged with “ultralong” CDR3s discovered in cows. The ultralong CDR3s comprise a knob on a stalk protruding from the antibody surface. The knob is a newly discovered diversity domain emerging from CDR3 of the otherwise canonical antibody structure in bovines. Rich with cysteines, the new domain has similar size to cytokines and other small proteins. Coupled with a human scaffold and using our humanized library approach above, we expect these ultralong CDR3s will facilitate antibody discovery to new families of therapeutic targets, including GPCRs, ion channels, and other intra-membrane therapeutic targets on the cell surface. Humanized IgG scaffolds that accommodate ultralong CDR3s may also impart antibody-like pharmacokinetics and pharmacodynamics to small proteins with desirable therapeutic properties. Preclinical leads include antibodies against ion channels for inflammatory disorders.
Senesco has recently acquired the Chimerasome technology, a multivalent protein nanocage scaffold that enables both surface decorations with high densities of biologics (such as antibodies) and encapsulation of a wide variety of payloads. The Chimerasome technology is currently under exploration for integration into the Senesco screening product engine as well as targeted delivery of drug payloads.