Document text
Principal Investigator: David Scott Johnson
Organization: GIGAMUNE, INC.
Fiscal Year: 2023
Award: $295,294
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
PROJECT SUMMARY
Project Title: Delivery of Full Length Dystrophin to Muscle Cells for DMD Gene Therapy
Organization: GigaMune Inc.
PI: David Johnson, Ph.D.
Duchenne’s muscular dystrophy (DMD) is a severe, incurable, X-linked recessive disorder resulting in chronic
muscle wasting caused by any of >7,000 mutations in the dystrophin gene. Wheelchair dependency typically
starts around 12 years, assisted ventilation is generally required by 20 years, and life expectancy is about 27
years. Unfortunately, dystrophin is very large, comprising 3,685 amino acids and an mRNA of 14kb, complicating
delivery of complete dystrophin via adeno-associated virus (AAV), which is limited by a strict payload limit of 5kb.
The ideal gene therapy for DMD would be long-term replacement of the complete dystrophin protein. One option
other than AAV would be lentivirus (LV), which has been used to deliver full-length dystrophin in vitro. GigaMune
has developed a novel next-generation LV platform (GigaLentiTM) for in vivo delivery of any gene to any cell in
vivo. The basis of GigaLentiTM is an abrogated fusogenic pseudotype which leverages cell-surface targeting by
an antibody fragment (scFv) for highly efficient, cell type-specific gene delivery.
We have engineered GigaLentiTM to specifically deliver gene payloads to T and B cells in vitro, but we have not
yet engineered muscle-specific LVs. The Specific Aim of this Phase I SBIR project is to use in vitro models to
develop a novel lentiviral technology for efficient and specific delivery of the full-length dystrophin gene to muscle
cells for modulation of DMD.
Terms: <Acceleration><Address><Adeno-Associated Viruses><American><Amino Acids><Anti-Sense Oligonucleotides><Antibody Fragments><Antisense Agent><Antisense Oligonucleotides><Automobile Driving><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><Binding><Biotech><Biotechnology><CRISPR approach><CRISPR based approach><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR tools><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/CAS approach><CRISPR/Cas method><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Cardiac Muscle Cells><Cardiac Myocytes><Cardiocyte><Cas nuclease technology><Cell Body><Cell Surface Proteins><Cell surface><Cells><Chronic><Clinical><Clustered Regularly Interspaced Short Palindromic Repeats approach><Clustered Regularly Interspaced Short Palindromic Repeats method><Clustered Regularly Interspaced Short Palindromic Repeats methodology><Clustered Regularly Interspaced Short Palindromic Repeats technique><Clustered Regularly Interspaced Short Palindromic Repeats technology><Control Groups><DNA Therapy><Dependence><Dependoparvovirus><Dependovirus><Disease><Disorder><Doctor of Philosophy><Dose><Drugs><Duchene><Duchenne><Duchenne muscular dystrophy><Duchenne-Griesinger syndrome><Dystrophin><Economics><Ellis-van Creveld (EvC) syndrome><Engineering><Exons><Gene Delivery><Gene Transfer Clinical><Genes><Genetic Alteration><Genetic Change><Genetic Intervention><Genetic defect><Grant><Guide RNA><Heart Muscle Cells><Heart myocyte><Human><Immunoglobulin Fragments><In Vitro><Integrin alpha Chains><Integrin alpha Subunits><Integrin α Subunits><Jobs><Length><Lentivirinae><Lentivirus><Life Expectancy><Link><Medication><Messenger RNA><Methods><Modern Man><Molecular Interaction><Muscle><Muscle Atrophy><Muscle Cells><Muscle Fibers><Muscle Tissue><Muscular Atrophy><Mutate><Mutation><Myocytes><Myotubes><Nature><Occupations><Paper><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Ph.D.><PhD><Pharmaceutic Preparations><Pharmaceutical Preparations><Phase><Pre-mRNA><Production><Professional Positions><Proteins><Pseudohypertrophic Muscular Dystrophy><Publishing><RNA, Messenger, Precursors><Rhabdomyocyte><SBIR><Skeletal Fiber><Skeletal Muscle><Skeletal Muscle Cell><Skeletal Muscle Fiber><Skeletal Myocytes><Small Business Innovation Research><Small Business Innovation Research Grant><Specificity><T-Cells><T-Lymphocyte><Technology><Testing><Therapeutic><Training><Transcript><Tropism><Variant><Variation><Voluntary Muscle><Wheel Chairs><Wheelchairs><Work><X-linked dilated cardiomyopathy><X-linked muscular dystrophy><X-linked recessive muscular dystrophy><adeno associated virus group><alpha Integrins><aminoacid><anti-sense agent><anti-sense oligo><antisense oligo><benign X-linked recessive muscular dystrophy><birth complications><cardiomyocyte><cell transduction><cell type><cellular transduction><childhood pseudohypertrophic muscular dystrophy><classic X-linked recessive muscular dystrophy><delivery complications><driving><drug development><drug/agent><economic><gRNA><gene repair therapy><gene therapy><gene-based therapy><genetic therapy><genome mutation><genomic therapy><immunogenicity><improved><in vitro Assay><in vitro Model><in vivo><lipid based nanoparticle><lipid nanoparticle><mRNA><mRNA Precursor><mild X-linked recessive muscular dystrophy><mobile assistance device><mobile assistance system><mobile assistive device><mobile assistive system><mouse model><murine model><muscle breakdown><muscle degradation><muscle deterioration><muscle engineering><muscle loss><muscle pharmacology><muscle wasting><muscular><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><patient oriented outcomes><patient population><progressive muscular dystrophy of childhood><promoter><promotor><pseudohypertrophic adult muscular dystrophy><pseudohypertrophic muscular paralysis><thymus derived lymphocyte><transduced cells><transduction efficiency><ventilation><α-Integrins>