Recently, much of our work has focused on editing and manipulating T-Cells to fight cancer using CRISPR technologies. Also, current work is targeting the development of vaccines and therapeutics for the novel coronavirus.
Ligandal delivers gene therapies exactly where they need to go.
ligand - a molecule that binds to another (usually larger) molecule.
Ligandal does this by harnessing the power of ligands, biomolecules that stick to other biomolecules, binding to the precise receptor profiles of targeted cell populations. Using a combination of computational techniques, state-of-the-art robotics and a unique nanomaterials platform, Ligandal is able to create extremely tailored gene therapy approaches.
Ligandal's goal is to create a platform for targeting specific cells, tissues and organs and genetically reprogramming our biology to be free of disease, ushering in a new era of genetically tailored, super-personalized medicine with minimal side effects.
ligand - a molecule that binds to another (usually larger) molecule.
Ligandal does this by harnessing the power of ligands, biomolecules that stick to other biomolecules, binding to the precise receptor profiles of targeted cell populations. Using a combination of computational techniques, state-of-the-art robotics and a unique nanomaterials platform, Ligandal is able to create extremely tailored gene therapy approaches.
Ligandal's goal is to create a platform for targeting specific cells, tissues and organs and genetically reprogramming our biology to be free of disease, ushering in a new era of genetically tailored, super-personalized medicine with minimal side effects.
Changing what medicine means.
Ligandal is creating a peptide-based, bioinspired material derived delivery approach that can be used for both transient and permanent gene therapy approaches, including delivery of gene editing tools such as CRISPR and raw genetic instructions such as mRNA and DNA.
By coupling arbitrary gene therapy modalities to personalized cell targeting systems, Ligandal creates cell-specific reprogramming instructions for any range of applications and will enable the biotechnology industry to adopt gene therapy at a global scale.
Using targeting peptides delivering CRISPR ribonucleoproteins (RNP), we have achieved up to 34% efficient editing of the TRAC locus in unstimulated primary human T cells. This is just the start of what we are aiming to do.
We can screen hundreds of formulations per day, each tailored to a given cell type's proteomic surface profile, while our state-of-the-art characterization laboratory allows us to rapidly permutate in a way that has never been seen before in the industry.
By coupling arbitrary gene therapy modalities to personalized cell targeting systems, Ligandal creates cell-specific reprogramming instructions for any range of applications and will enable the biotechnology industry to adopt gene therapy at a global scale.
Using targeting peptides delivering CRISPR ribonucleoproteins (RNP), we have achieved up to 34% efficient editing of the TRAC locus in unstimulated primary human T cells. This is just the start of what we are aiming to do.
We can screen hundreds of formulations per day, each tailored to a given cell type's proteomic surface profile, while our state-of-the-art characterization laboratory allows us to rapidly permutate in a way that has never been seen before in the industry.
CRISPR must enter a cell's nucleus to perform its function. Shown is super-resolution microscopy (courtesy of UC Berkeley) of CRISPR ribonucleoprotein (RNP) delivery into the nucleus of a human primary T-cell utilizing Ligandal's cell-specifically targeted gene editing nanomaterials. Green: CRISPR RNP. Blue: nucleus. Red: actin. Scale bar = 500 nanometers.
Shown are Ligandal's peptide-mediated CRISPR gene editing efficiencies of the T cell receptor's TRAC locus in a mixture of CD4+ and CD8+ unstimulated human T cells treated with 54 unique formulations of Ligandal's materials, as measured via Sanger sequencing. Nucleofection controls are shown in wells C11 - F11. Chemically modified gRNA was provided by Synthego. Extended data may be viewed here: https://ice.synthego.com/#/analyze/results/xxz7nu1jm2yttq9q
Shown is Cas9-EGFP (Cas9+) and AF647-tagged peptide (NP+) live cell uptake 1 day post-transfection in unstimulated primary human T cells for CD4+ (top) and CD8+ (bottom) subpopulations grown in co-culture and treated with 90 unique formulations of Ligandal's materials. Measurements were performed with an Attune NxT flow cytometer.
Nucleofection + Lipofection controls are shown in wells G11 for EGFP-Cas9-NLS and F11 for NLS-Cas9-NLS. Negative controls are shown in well H11. Controls lacked the AF647 tag (NP+ tag), however were 26% and 13% CRISPR-EGFP+ at 24h post-transfection for CD4+ and CD8+ subpopulations, respectively, with treatment with Lipofectamine CRISPRMAX followed by nucleofection.
Lipofectamine CRISPRMAX does not perform in these cell types without subsequent nucleofection (data not shown).
Nucleofection + Lipofection controls are shown in wells G11 for EGFP-Cas9-NLS and F11 for NLS-Cas9-NLS. Negative controls are shown in well H11. Controls lacked the AF647 tag (NP+ tag), however were 26% and 13% CRISPR-EGFP+ at 24h post-transfection for CD4+ and CD8+ subpopulations, respectively, with treatment with Lipofectamine CRISPRMAX followed by nucleofection.
Lipofectamine CRISPRMAX does not perform in these cell types without subsequent nucleofection (data not shown).
THE CURRENT STAGE OF DEVELOPMENT.
Ligandal is developing a set of proprietary immunotherapies and hematological gene therapies.
Ligandal has established methods, protocols, formulations and foundational intellectual property for rapidly designing, synthesizing, screening, optimizing and scaling nanoformulations for virtually any gene therapy application. Ligandal has demonstrated a robust capacity to target specific blood and bone marrow cells (e.g. T-cells, hematopoietic stem cells) and deliver one or more sets of permanent or transient genetic instructions to those cells.
Ligandal has established methods, protocols, formulations and foundational intellectual property for rapidly designing, synthesizing, screening, optimizing and scaling nanoformulations for virtually any gene therapy application. Ligandal has demonstrated a robust capacity to target specific blood and bone marrow cells (e.g. T-cells, hematopoietic stem cells) and deliver one or more sets of permanent or transient genetic instructions to those cells.
UNIQUE IN THE MARKETPLACE.
Viruses cost as much as $10,000s per milligram to manufacture at clinical scale. Ligandal's non-viral approaches aim to reduce the cost of gene therapy manufacturing 100x.
Unlike lipid and PEGylated particles, our materials are entirely derived from proteins and can be customized for any cellular targeting application or payload. Additionally, our materials are serum-stable, enabling in vivo applications.
Ligandal's team has invested seven years into foundational R&D surrounding a unique capacity for screening and developing cell targeting ligands that can directly and instantaneously couple to gene editing tools such as CRISPR, as well as transient gene therapy modalities such as DNA and mRNA.
Gene therapies are storehouses of cures. But what use is a storehouse without a delivery service? Ligandal is the delivery service that makes gene therapies real.
SUMMARY: A NEW PARADIGM FOR MEDICINE.Ligandal is developing the capability to deliver unique curative genetic therapies with personalized nanotechnology. Preclinical studies of Ligandal technology indicate that it will create unprecedented freedom to innovate in the hematology and immunotherapy sectors.
The company is also planning to apply its technology to additional disease verticals, including the broadest disease: aging. This will usher our world into an era of globally accessible regenerative medicine. |