# Immunopharmacology of FVIII Bioengineering and Gene Therapy

> **NIH NIH U54** · EMORY UNIVERSITY · 2020 · $343,223

## Abstract

Project 3: Immunopharmacology of FVIII Bioengineering and Gene Therapy
Summary
The development of inhibitory antibodies directed against human factor VIII remains the most significant clinical
complication associated with the treatment of hemophilia A and is a critical barrier to gene therapy approaches.
Therefore, improved understanding of the immunology and pharmacology related to promising liver-directed
adeno-associated viral (AAV) vector and hematopoietic stem cell (HSC)-directed lentiviral vector (LV) gene
therapy strategies is needed. The studies proposed in Project 3 of this U54 application are designed to advance
our knowledge of fVIII immunobiology in the context of these gene therapies. The proposed studies are designed
to i) analyze the molecular composition and immune reactivity of bioengineered recombinant infusion products
as well as liver-directed AAV and HSC-directed LV gene therapy derived fVIII, ii) identify critical design
parameters associated with immunogenicity and inhibitor eradiation potential of liver-directed AAV-fVIII gene
therapy and iii) evaluate the immunogenicity and inhibitor eradicating potential of non-genotoxic HSC-directed
LV gene therapy protocols. These studies will take advantage of available fVIII, glycomics, structural biology,
immunology and gene therapy expertise as well as diverse state-of-the-art technologies, including our recently
described in silico codon-optimization, synthetic promoter engineering and ancestral sequence reconstruction
technology, to improve the current understanding and better assess the overall potential for gene therapy to
address all hemophilia A patient populations including those with fVIII inhibitors.

## Key facts

- **NIH application ID:** 9930145
- **Project number:** 5U54HL141981-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Christopher Bradley Doering
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,223
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930145

## Citation

> US National Institutes of Health, RePORTER application 9930145, Immunopharmacology of FVIII Bioengineering and Gene Therapy (5U54HL141981-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9930145. Licensed CC0.

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