# A novel rabbit model for easy monoclonal antibody production

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $195,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Monoclonal antibodies (mAbs) and mAb-derived antibody therapeutics, are currently widely used to treat
human diseases, such as cancer and autoimmune diseases. Although the rabbit as a platform to producing
polyclonal antibodies has been utilized for a long time, generation of rabbit monoclonal antibodies has been
limited by difficulties in generating stable hybridomas. The adoption of molecular cloning of Ig genes directly from
B cells followed by expression in cell culture has introduced new life in the rabbit monoclonal field. However, the
efficiency of mAb production is still low and the type of mAbs available from rabbit limited. Recently, we reported
that deficiency in the Transmembrane Activator and CAML Interactor (TACI), a receptor that controls plasma cell
differentiation, also causes marked expansion of antigen-responsive germinal center (GC) B cells enhancing
affinity maturation and facilitating production of high-affinity IgG. TACI-deficiency also increased the yield of
monoclonal antibody production by the hybridoma technique. In the present application, we propose to abrogate
expression of TACI in the rabbit germline with the goal of enhancing monoclonal antibody production.
 We have established a highly efficient rabbit genome editing platform using CRISPR/Cas9 technology.
We now propose to target the rabbit TACI gene by CRISPR/Cas9 technology to produce a TACI-KO rabbit. We
will use the well-established platform to first generate TACI mutant rabbit founders. These founders will be tested
for germline transmission, and if so, to establish heterozygous TACI mutant animals, followed by breeding to
obtain homozygous TACI mutant animals. We will test the hypothesis that TACI-deficiency in rabbits will
enhance mAb production and the affinity and specificity of those antibodies. We propose to establish TACI-
deficient rabbits as a superior bio-reactor for mAb production.

## Key facts

- **NIH application ID:** 10105896
- **Project number:** 1R21GM140359-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** MARILIA Isabel CASCALHO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,000
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10105896

## Citation

> US National Institutes of Health, RePORTER application 10105896, A novel rabbit model for easy monoclonal antibody production (1R21GM140359-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10105896. Licensed CC0.

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