De novo-designed pMHC binders facilitate T cell-mediated cytotoxicity toward cancer cells.

The recognition of intracellular antigens by CD8 T cells through T cell receptors (TCRs) is central for adaptive immunity against infections and cancer. However, the identification of TCRs from patient material remains complex. We present a rapid de novo minibinder (miBd) design platform leveraging state-of-the-art generative models to engineer miBds targeting the cancer-associated peptide-bound major histocompatibility complex (pMHC) SLLMWITQC/HLA-A*02:01 (NY-ESO-1).

Structural mechanisms behind the neutralisation of long-chain α-neurotoxins by broadly neutralising VHs discovered using a consensus antigen.

Snakebite envenoming, a neglected tropical disease, affects millions globally, causing significant morbidity and mortality. Developing broadly neutralising monoclonal antibodies offers a promising approach to address the antigenic variation present in snake venoms. In this study, we designed a long-chain consensus α-neurotoxin, LCC, to serve as an antigen in a phage display-based antibody discovery campaign.

Discovery of broadly neutralizing VHs against short-chain α-neurotoxins using a consensus toxin as an antigen.

Snakebite envenoming is a neglected tropical disease that afflicts millions of people globally, leading to substantial morbidity and mortality. Developing novel antivenoms, particularly recombinant antivenoms based on broadly neutralizing monoclonal antibodies, offers a promising strategy to address the challenge posed by venom variability. However, the extensive diversity of snake venom toxins across species and geographical regions makes this goal inherently complex.

Post-assembly Plasmid Amplification for Increased Transformation Yields in and .

Many biological disciplines rely upon the transformation of host cells with heterologous DNA to edit, engineer, or examine biological phenotypes. Transformation of model cell strains () under model conditions (electroporation of circular supercoiled plasmid DNA; typically pUC19) can achieve >10 transformants/μg DNA. Yet outside of these conditions, e.

De novo designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors, resulting in life-threatening neurotoxicity. At present, the only available treatments for snakebites consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

V-ToCs (Venom Toxin Clustering): A tool for the investigation of sequence and structure similarities in snake venom toxins.

Recently, there has been a major push toward the development of next-generation treatments against snakebite envenoming. However, unlike current antivenoms that rely on animal-derived polyclonal antibodies, most of these novel approaches are reliant on an in-depth understanding of the over 2000 known snake venom toxins. Indeed, by identifying similarities (i.

designed proteins neutralize lethal snake venom toxins.

Snakebite envenoming remains a devastating and neglected tropical disease, claiming over 100,000 lives annually and causing severe complications and long-lasting disabilities for many more. Three-finger toxins (3FTx) are highly toxic components of elapid snake venoms that can cause diverse pathologies, including severe tissue damage and inhibition of nicotinic acetylcholine receptors (nAChRs) resulting in life-threatening neurotoxicity. Currently, the only available treatments for snakebite consist of polyclonal antibodies derived from the plasma of immunized animals, which have high cost and limited efficacy against 3FTxs.

Deep mutational learning predicts ACE2 binding and antibody escape to combinatorial mutations in the SARS-CoV-2 receptor-binding domain.

The continual evolution of SARS-CoV-2 and the emergence of variants that show resistance to vaccines and neutralizing antibodies threaten to prolong the COVID-19 pandemic. Selection and emergence of SARS-CoV-2 variants are driven in part by mutations within the viral spike protein and in particular the ACE2 receptor-binding domain (RBD), a primary target site for neutralizing antibodies. Here, we develop deep mutational learning (DML), a machine-learning-guided protein engineering technology, which is used to investigate a massive sequence space of combinatorial mutations, representing billions of RBD variants, by accurately predicting their impact on ACE2 binding and antibody escape.

SARS-CoV-2 reactive and neutralizing antibodies discovered by single-cell sequencing of plasma cells and mammalian display.

Characterization of COVID-19 antibodies has largely focused on memory B cells; however, it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in resolving SARS-CoV-2 infection. Little is known about the specificity of plasma cells, largely because plasma cells lack surface antibody expression, thereby complicating their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and mammalian display to interrogate the specificity of plasma cells from 16 convalescent patients.