National Technology & Engineering Solutions of Sandia, LLC

Yooli Kim Light

Brooke Nicole Harmon

Chung-Yan Koh

Maxwell Stefan

Anup Kumar Singh

Joseph S Schoeniger

Robert Meagher

Cameron Scott Ball

Matthew Ernest Piccini

Jennifer Lauren Schwedler

Catherine Margaret Mageeney

Le Thanh Mai Pham

Edwin A Saada

Mary Bao Tran-Gyamfi

Kenneth Sale

Christine Elizabeth Thatcher

Christopher Sumner

Kyle Jeffrey Seamon

Peter Riches McIlroy

Disclosed herein are single-domain antibodies (sdABs) configured for targeting to human or mammalian lung tissue. Constructs and methods of using such sdABs are also described herein, such as methods of binding with and transporting other sdABs or other cargo with beneficial functionalities, binding to and transporting biochemical or pharmaceutical species with beneficial functionalities, and a method of treating, diagnosing, or prophylactically treating a disease, condition, or malignancy. A purification method for in vivo treatment or testing is also provided.

Lung-targeting single-domain antibodies and purification methods

Provided herein are single domain antibodies (sdAbs) configured for passing the blood brain barrier in a human or mammal brain. Methods of using such sdAbs are also described herein, such as methods of binding to brain cells, binding with and transporting other sdAbs with beneficial functionalities, binding to and transporting biochemical or pharmaceutical species with beneficial functionalities, and treating, diagnosing, or prophylactically treating a disease, malignancy, or condition.

Brain-targeting single domain antibodies and purification methods

Provided herein are asymmetric biparatopic neutralizing nanobody-based antibodies which engage SARS-2 spike in at least two independent epitopes. Several biparatopic constructs showed synergy in neutralizing viral infection of cells. Data also showed that single biparatopic constructs are more effective than the combination of the parental monotopic constructs were at neutralization. The nanobodies that were identified in an initial screen of a large and highly diverse library bind to a single epitope that overlaps with the ACE2 binding site.

Multivalent anti-SARS-CoV-2 nanobodies

A large and highly diverse nanobody library was constructed and screened against multiple variants of SARS-COV-2 to find nanobodies with high sensitivity and specificity for the variants. Four rounds of positive selection against a panel of six diverse SARS-COV-2 variant RBDs was performed with our high-diversity. At least 59 of these nanobodies were found to work well against Alpha, Beta, Gamma, Delta, Kappa, Lambda and Mu with some overlap efficacy against other variants. These nanobodies have efficacy as stand-alone nanobodies and as a construct comprising nanobodies linked to the human IgG1 constant fragment (Fc) (nanobody-hFc constructions or nb-hFcs) to make enhanced humanized sdAbs with all the attributes of nanobodies with improved half-life and optimized effector functions. Several promising nanobodies that neutralize the original SARS-COV-2 and several of its variants have been identified, including Delta, with high efficacy. In particular, a subset of these nanobodies bind to the Omicron RBD.

SARS-CoV-2 variant nanobodies and constructs comprising such nanobodies

The present disclosure relates to an isolated or purified antibody, or a fragment thereof, having a binding domain that binds to a coronavirus (e.g., SARS-COV-2) or a portion thereof. In other embodiments, the antibody includes a binding domain that competes with binding to angiotensin converting enzyme 2 (ACE2) or a portion thereof. Methods of using such antibodies are also described herein, such as methods of treating or delaying the progression of a disease associated with a coronavirus.

Coronavirus neutralizing humanized antibodies and uses thereof

Specific and broad-spectrum inhibitory peptides to CRISPR Cas9 variants (SpyCas9, SauCas9, and CjeCas9) are disclosed. A method of making and using these peptides with therapeutic CRISPR Cas9 (to improve desired targeting) or against harmful CRISPR Cas9 components (already active in a patient) is also disclosed. The peptides combined with a delivery system is also disclosed.

Peptide inhibitors of CRISPR-Cas9

The present invention relates, in part, to methods for detecting nuclease activity, such as the activity of Cas nucleases. Also described herein are compositions for conducting assays, as well as methods for conducting assays in the presence of test compounds.

CRISPR/Cas activity assays and compositions thereof

The present invention relates to probes and primers beneficial for conducting amplification assays, such as those including loop-mediated isothermal amplification reactions. Also described herein are methods for detecting targets using such probes and/or primers.

Endpoint detection of amplified nucleic acids

Embodiments of the present invention are directed toward devices, systems, and methods for purifying nucleic acids to conduct polymerase chain reaction (PCR) assays. In one example, a method includes generating complexes of silica beads and nucleic acids in a lysis buffer, transporting the complexes through an immiscible fluid to remove interfering compounds from the complexes, further transporting the complexes into a density medium containing components required for PCR where the nucleic acids disassociate from the silica beads, and thermocycling the contents of the density medium to achieve PCR. Signal may be detected from labeling agents in the components required for PCR.

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Pleasanton, CA, United States of America

Yooli Kim Light