Alicanto:Proteogenomic discovery of single chain antibodies in llama

Antibodies are a key component of the adaptive immune systemreleased in response to disease in order to target foreign molecular surfacesDue to their capacity for high target affinity and specificitythey ve become one of the fastest growing classes of therapeutic molecules addressing a range of disease including infectious diseasesauto immune diseasesand cancerCamelidsincluding llamascamelsand alpacasproduce a unique repertoire of antibodies that includes both dual chain antibodies and single chain antibodiesSingle chain antibodiesdue to their comparative structural simplicityare simpler to express and develop at the scale required for therapeuticsIn additionsingle chain antibodies are able to bind to small epitopessuch as enzyme active sitesthat would be hidden to largerdual chain antibodiesThe binding domain of the single chain antibody may be small enough to infiltrate traditionally difficult to access tissuesincluding crossing the blood brain barrierCurrent approaches to single chain antibody discovery require the collection of cells that encode the antibody genesincluding memory B cells and plasma cellsTarget specific antibodies are selected after the antibody transcripts are cloned into a display systemsuch as phage or yeastWhile memory B cells and plasma cells represent only a minute fraction of the cells located in peripheral bloodtargetspecific antibodies are present in high concentration in blood after an infectionEach plasma cell can secrete thousands of antibodies per minuteDigital Proteomics is developing Alicantoa technology that utilizes the antibodies circulating in blood to identify target specific antibodiesAlicanto integrates two sources of information about the antibody repertoireFirstAlicanto constructs a database of potential antigen specific antibodies by performing next generation sequencing of antibody transcriptsNextAlicanto enriches for target specific antibodies from the blood using affinity chromatography and subjects the antibodies to tandem mass spectrometryFinallyAlicanto uses machine learning models to integrate the sequencing and mass spectrometry data to derive a collection of target specific antibody candidatesFor single chain antibody discoveryAlicanto will use specialized primers and enrichment techniques to isolate only the subset of the antibody repertoire that contains the single chain antibodiesAlicanto will be used to discover high affinitysingle chain antibodies for development as therapeutic molecules Antibodies are produced natively in humans to fight disease and the molecules have garnered significant attention due to their therapeutic potentialSingle chain antibodieswhich are smaller than conventional antibodiesrepresent a new frontier for antibody based therapeutics due to their ability to target molecular surfaces that would be hidden to larger antibodiesas well as the relative simplicity of their developmentDigital Proteomics is developing Alicanto to discover single chain antibodies in llama that can be developed into human therapies