Nectagen is enthusiastic about collaborating with academic labs and companies that have expertise complementary to ours. For Nectagen’s part, we can readily contribute well-characterized nanoCLAMPs, variants, and their targets for proof-of-concept studies. In areas of high interest, we can and have designed and implemented screens to isolate nanoCLAMPs with specific performance characteristics. Nectagen has served as the grantee or sub-awardee on multiple NIH grants awarded to us or our non-profit or for-profit collaborators.
Areas of Interest
Rationale. nanoCLAMPs have a distinctive combination of properties with potential utility in biosensor applications. nanoCLAMPs based on our 2nd generation scaffold are typically well suited to applications in extreme environments because of their resistant to heat, proteases, alkali and organic solvent. In addition, their high affinity, monomeric binding may be well suited to some biosensor formats in either capture or detection mode. Finally, their high negative charge may also improve performance in some biosensor formats. nanoCLAMPs’ properties have the potential to support the development of biosensors that have improved sensitivity, are easier to manufacture or maintain their performance in challenging environments. For instance, our collaborators have used nanoCLAMPs as a component of an electrochemical biosensor to measure methorexate (Guo Nature Communications 2021). In addition, Nectagen has also isolated nanoCLAMPs selectively recognizing the SARS-CoV-2 receptor binding domain with low pM dissociation constants. Our collaborators are using these nanoCLAMPs to develop field effect transistors for detecting coronavirus in clinical samples.
- Typical nM monomeric dissociation constants (high pM possible after affinity maturation, low pM avidity possible via multimerization)
- High and uniformly distributed negative charge (typical pI range of 4 to 4.5)
- Compatible with 100% organic solvent and heat treatment during manufacture
2. Diagnostics for Point-of-Care or Low Resource Settings
Rationale. nanoCLAMPs' robust properties provide advantages for transport, storage and use in point-of-care or low resource settings. nanoCLAMPs are readily lyophilized and rehydrated without the need for any unusual excipients. With melting temperatures are typically at least >60°C and often >100°C, nanoCLAMPs do not need a cold chain for transport even when in solution. Affinity resins with nanoCLAMP capture agents based on the first generation scaffold have not shown any detectable degradation in performance after more than 5 years of refrigerated storage. Less stability data is available for 2nd generation nanoCLAMPs but they are expected to have the same or higher shelf-life based on their improved robustness and amino acid composition.
- Long shelf life (>5 yr.)
- Amino acid composition minimizing oxidation and deamidation (no methionine or cysteine and 1 asparagine)
- Maintenance of activity after exposure to boiling
- Readily lyophilized and reconstituted
3. Hydrogels and Other Biomaterials
Rationale. nanoCLAMPs robustness, tunability and architecture have the potential to add distinctive functionality to hydrogels or other biomaterials. nanoCLAMPs’ thermostability, including resistance to autoclaving, makes them compatible with thermoforming or other heat-based procedures. nanoCLAMPs’ compatibility with organic solvents such as 100% DMF makes them suitable for a broader range of manufacturing, loading and extraction procedures. Nectagen also has a collection of temperature-sensitive and protease-sensitive mutations that enable the adjustment of stability and release by temperature or proteases. Finally, nanoCLAMPs N- and C- termini are adjacent to each other and distant from the binding face. Because of this architecture, nanoCLAMPs typically maintain function when inserted in a loop or at either end of polymerizing proteins.
Potential benefits for hydrogels or other biomaterials
- Compatible with thermoforming
- Compatible with organic solvents used for manufacture, loading or extraction
- Tunable release via combinations of temperature- and/or protease-sensitive mutations
- Flexible insertion/fusion sites because of adjacent N- and C-termini
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If you are interested in these or other areas for collaboration, please contact Nectagen’s Director of Research, Dr. Richard Suderman, via the contact form.