Production and Characterization of Human Immunoglobulin Producing Goats for Diagnostic Reagents and Therapeutics

Project Summary
A research plan is proposed to engineer goats that produce fully human immunoglobulinThese animals will be
evaluated as a candidate platform system for production of both targeted therapeutic immunoglobulin as well as
reagent antibodies for standards and controls of serological assays of human clinical samplesPrevious studies
have demonstrated that ungulates such as cattle can produce large amounts of human immunoglobulins and
show extremely high titers and neutralizing antibody activities against various antigensincluding infectious
diseasestoxins and other targets following multiple immunizationsIn this studySAB Capra LLCSABand
Utah State University intend to expand and optimize this technology by producing transchromosomicTcgoats
containing a human artificial chromosome vectorHACwhich contains the entire germline repertoire of the
human antibody genesIn additionthe participants will produce goat fibroblast cell lines where the endogenous
goat antibody genes will be silenced using current gene editing technologiesThere are three specific aims in
this projectdevelop the first human immunoglobulin producing Tc goats by transferring the HAC containing
the germ line human antibody heavy and light chain genes to KO fetal fibroblast cell linesevaluate and
characterize human immunoglobulin produced in the Tc goats from Aimand determine the stability and
antibody production of the Tc goats and compare the immunoglobulin response to Tc cattle as well as humansproduce high titer targeted immunoglobulin to pandemic flu strainsH Nand or H Nfor target specific
evaluationData generated from this study will enable further work to be conducted to determine the usefulness
of small ungulates producing human antibodies used as production animals to produce targeted human
immunoglobulin therapeutic candidates and diagnostic standards and controls to emerging diseasesIf this
project is completed successfullyit will also have a broad implication that SAB s platform technology can be
used in both a largecattleand smallgoatungulate species providing greater flexibility in producing product
candidatesThe addition of a small ungulate species will reduce costs associated with generating antibodies for
small volume products as well as targeted human immunoglobulins used as diagnostic standards and controls
for testing human clinical samples Project narrative
Goats that produce fully human immunoglobulin will be produced and evaluated as a candidate system for
production of both therapeutic immunoglobulin as well as reagent antibodies for standards and controls of
serological assays of human clinical samplesUpon successfully completing this projectthese animals will be
used to produce hyperimmune targeted immunoglobulin against infectious diseasetoxinsoncology targetsauto immune targets and inflammation targetsThis will provide an additional platform technology that can be
used to address global unmet medical needs in a rapid and easily scalable production system leading to
therapeutics to a wide variety of diseases