GenScript Life Science
Research Grant Program

What We Do

MOMM Diagnostics develops high-sensitivity rapid diagnostic tests. MOMMs proprietary technology opens previously laboratory-based test for in clinic- and self-testing. Our first test in development is preXclude - a rapid test for preeclampsia, offering unprecedented sensitivity at the point-of-care. Preeclampsia is a significant health problem accounting for a third of obstetric costs (over 2 Billion USD) in the US alone. It affects 2-8% of all pregnancies worldwide and can lead to severe short- and long-term complications for both mother and baby. preXclude delivers immediate information to doctors during a pregnancy check-up helping them optimize treatment and reduce the stress and anxiety for expectant mothers.

How GenScript LSRG Helps

The money granted in the MOMMscript project will enable MOMM Diagnostics to utilise GenScript’s expertise in recombinant antibody development and manufacturing to secure the supply of highly sensitive and specific affinity reagents.

What We Do

The proteins in the AAA+ superfamily of ATPases are often described as molecular machines because they form oligomeric structures that harness chemical energy derived from ATP hydrolysis to perform mechanical works on proteins or nucleic acids. These molecular machines are found in all kingdoms of living organisms, and they have evolved to perform different functions, thereby participating in diverse cell regulation processes. My research is focused on elucidating the structural basis for the functions of these molecular machines, by understanding how their oligomeric structures and biochemical properties are coupled together. Many of the AAA+ proteins in higher organisms have evolved from bacterial ancestors with a significantly expanded ATPase region and form supramolecular complexes in cells. Investigating these megadalton complexes poses challenges, demanding innovative approaches such as gene constructs tailored for effective protein purification.

How GenScript LSRG Helps

I am excited about leveraging support from the LSRG-funded gene synthesis service to significantly advance these investigations.

What We Do

Adeno-Associated Viruses (AAVs) are the leading tool in current gene therapy. However, immune responses to AAVs limit their efficacy, reduces patient eligibility, and constitute a major limitation of their therapeutic application.

In this project, we leverage generative AI-based protein design to explore novel AAV capsids able to evade pre-existing immunity. To test the efficacy of infection of our in-silico designs, and to further train the model, we combined directed evolution of chimeric capsids and de novo capsid design. We then tested these new libraries using high-throughput methods in multiple cellular models, such as HEK293T and HepG2, both in presence and in absence of patient-derived sera. Testing with patient-derived sera reports on the ability of novel AAV capsids to evade pre-existing neutralizing antibodies that would decrease therapeutic efficacy.

By iterating generative modeling and screening with sera from a diverse population, we anticipate the discovery of capsid sequences with high probability of correct folding, high immune-evasion potential and a wide applicability across multiple ethnic groups.

How GenScript LSRG Helps

“Thanks to the LSRG grant, we could expand our repertoire of de novo synthesis to 100 synthetic sequences, and have them all synthesized and shipped to us. An endeavor otherwise not possible for an academic lab.”

“The LSRG grant enabled us to pursue two parallel strategies and effectively de-risk our original approach”

What We Do

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, projected to affect 288 million people worldwide by 2040 due to the growing ageing population. Neovascular AMD (nAMD), the most severe form, leads to sudden central vision loss, caused by leaky blood vessels that bleed into the retina, causing tissue damage and scarring. The rapid onset and demographic of AMD result in high social and healthcare costs.

Although anti-VEGF therapies have revolutionized nAMD treatment, they involve frequent eye injections every 6-8 weeks that is burdensome and unpleasant for patients and caregivers, significantly impacting their quality of life. Importantly, a significant proportion of eyes with nAMD develop retinal/macular scarring and these eyes respond very poorly to anti-VEGF therapies with respect to preservation of vision.

Ikarovec is developing IKC203V, an AAV-based ocular gene therapy for nAMD. IKC203V encodes two secreted proteins: an Fc-fusion protein to neutralise VEGF, a key driver of neovascularisation and a single-chain variable fragment (ScFv) to neutralise CTGF, a key driver of fibrosis/scarring

The efficacy of the anti-CTGF component will be assessed in vivo using an optimised 2-stage laser CNV subretinal fibrosis model, and screened against other anti-fibrotics.

How GenScript LSRG Helps

We are thrilled to be working with GenScript to advance the development of our gene therapy. We have a long-standing relationship with GenScript in relation to plasmid cloning, and we are excited to try their vector manufacture services. This grant has allowed Ikarovec to expand our in vivo anti-fibrotic evaluation, which in turn will help complete a full data package suitable for clinical development.

What We Do

The main focus of our lab is on antibody discovery and characterization, especially for infectious diseases-associated pathogens, including hypervariable viruses such as influenza virus, SARS-CoV-2 and hepatitis C virus (HCV).

More in detail, the lab is equipped with >15 years of research experience focused on the selection, cloning, characterization and engineering of monoclonal antibodies (mAbs), of human or animal origin, and directed against infectious agents. In particular, the potential of these mAbs is investigated as therapeutic molecules, able to directly neutralize infectious pathogens, or as indirect molecules to be exploited for the development of prophylactic approaches and for the modeling of the humoral immune response. Moreover, their possible engineering in order to improve (i.e., their binding or stability characteristics) or gain new functions (such as in the case of chimeric antigen receptors, CARs), represents a promising and alternative approach for difficult-to-eradicate infectious pathogens. In this context, we are committed also in the field of innovative prophylactic countermeasures for the purpose of improving or developing new vaccines for hypervariable pathogens. In particular, we are investigating the mechanisms of protection elicited by standard of care and next-generation influenza vaccines and adopting different strategies for the development of a vaccine against HCV.

How GenScript LSRG Helps

The LSRG-funded GenScript services will benefit the research of our lab for generating the necessary molecular tools for the assessment of the immune response elicited by our experimental HCV vaccines.

What We Do

The liver’s role in drug metabolism makes it an ideal candidate to use for in vitro drug screening applications. Human liver organoids (HLO) are three-dimensional tissue constructs that recapitulate native cell architecture and functionality and have immense potential for screening new pharmaceutical therapies. However, HLO generation heavily relies on Matrigel, an ill-defined tumor-derived extracellular matrix (ECM) that contributes to varied HLO formation and function. Due to these limitations, evaluating the toxicity of new pharmaceutics can be challenging. For this project, we plan to generate a defined synthetic matrix with controlled presentation of ECM biosignals and mechanical signals that can be used to reliably form HLO. Tailored alginate matrices will be used as the biomaterial for developing a defined ECM, as cells cannot adhere to native alginate, and its mechanical properties can be independently controlled by introducing additional functional groups. We plan to use tailored alginate matrices, whose ECM biomechanics can be independently controlled from the matrix biosignals, to determine what signals are inductive for liver tissue formation. This work will be a critical step in increasing our understanding of signals involved in the formation of the liver and provide a new biomaterial design platform for consistently generating organoids.

How GenScript LSRG Helps

The GenScript services will allow us to systematically evaluate what role matrix biosignals and mechanics have on liver organoid formation in our biomaterial system. This information may then be used to reliably generate liver tissue constructs in vitro.

What We Do

Living cells are intricate information processors. Unlike electronic computers that rely solely on electrical signals to process information, living cells use a complex network of interacting biochemical and biophysical signals to drive biological function and achieve biological computation. These signals include ion concentrations, molecular messenger levels, protein activities, and gene regulations. They form signal transduction networks in cells and collectively convert cellular inputs into cellular outcomes by interacting in complex ways. Subtle defects in these processes are associated with a wide range of diseases. We (UMich Spatial Biodynamics: spatialbiodynamics.org) are developing new molecular tools and imaging technologies to measure and analyze these cellular signals, to ultimately provide mechanistic insights into mammalian cellular processes in healthy and diseased states.

How GenScript LSRG Helps

The LSRG-funded gene synthesis and cloning service at GenScript will help us to generate new molecular constructs and accelerate our efforts to design and validate novel molecular tools.

What We Do

TargetGene, founded in 2012 in Israel, is a pioneer in the gene-editing field, propelled by its proprietary best-in-class platform known as T-GEE. T-GEE enables SAFE modification of the patient’s own DNA. With T-GEE, genes can be added, deleted, or precisely replaced—effectively rewiring the transcriptome. We thus intend to correct genetic abnormalities or enhance specific cell types, ultimately leading to cures rather than chronic treatments.

Leveraging the advantages of T-GEE, we’re driving innovations in the development of safe and effective cell therapies for cancer, cardiovascular and immune-related diseases. Our commitment extends to achieving both pre-clinical and clinical readiness.

Our novel and proprietary T-GEE programmable molecular “DNA scissors” utilizes two guides and an obligatory dimeric nuclease to achieve its exquisite specificity. T-GEE solves the biggest problem of gene editing - off-target cleavage of unintended genes- and is predicted to be orders of magnitude more precise than CRISPR-Cas9, potentially creating a radically safer therapeutic tool.

TargetGene has an exceptionally rich and broad patent portfolio including 15 granted patents and multiple patents pending. We are strategically partnering in different cell therapies and are also key partners in CAR-T REX, a major EU-funded consortium focused on CAR-T therapies for solid tumors.

How GenScript LSRG Helps

With the assistance of the LSR grant we hope to get preliminary data on novel methods to further enhance the T-GEE platform and to subsequently broaden our patent portfolio.

What We Do

T lymphocytes are powerful immune cells capable of combating severe infections and, under certain conditions, attacking healthy organs. Over the past decades, significant advancements have enabled us to effectively redirect these cells against cancer. This approach has achieved tremendous success, particularly in hematological cancers and, more recently, in the treatment of rheumatological diseases. However, the complexity of solid tumors presents a unique challenge, necessitating more precisely defined genetic programs and sophisticated genome engineering techniques. Our research leverages cutting-edge genome engineering, including large-scale CRISPR screening, to decode complex genetic networks within T cells. By systematically altering genes and observing the resultant changes in T cell behavior, we aim to unravel the intricate genetic interactions that govern T cell function and effectiveness. This knowledge will be instrumental in designing the next generation of cancer therapies, tailored to overcome the specific challenges posed by solid tumors. Additionally, we are investigating novel gene targets and regulatory elements that could enhance T cell persistence and anti-tumor activity. Our ultimate goal is to develop innovative therapeutic strategies that harness the full potential of T cells, thereby improving outcomes for patients with various cancer types and advancing the field of immunotherapy.

How GenScript LSRG Helps

The GenScript Life Sciences Grant will help us shortening our iteration cycles as we design and test genomic T cell alterations in the fight against cancer.

What We Do

Inherited bone marrow diseases impact 1 in 500 Canadians. Hematopoietic stem cell transplantation (HCT) can be curative, but is limited by factors such as socioeconomic barriers, appropriate donor availability, toxicities, and risks of graft-vs-host disease. While ex-vivo gene editing technologies of hematopoietic stem and progenitor cells (HSPCs) are promising they can be expensive, time consuming and require specialized manufacturing facilities. In-vivo gene therapy could overcome these limitations by circumventing the need for HCT. However, targeted delivery into HSPCs is a challenge. The focus of our research proposal is to develop protocols for direct in-vivo gene editing of HSPCs for treatment of monogenic illnesses.

How GenScript LSRG Helps

Funding from LSRG-funded GenScript grant will cover costs associated with tools (gene editing machinery) required for gene editing of HSPCs. 

What We Do

ProtOS is creating a generative AI based mRNA therapeutic development platform that designs coding mRNA sequences at the nucleotide level. These mRNA drugs code for expressible and functional proteins that discover and modulate disease pathways. Current proof-of-concept is focused on known cancer pathways, such as the MDM2-p53 interaction but scope may become wider in the medium term. 

Target discovery and lead development are done by in-silico design of binders to specific epitopes of proteins involved in disease. The development process involves iterative LNP-mRNA/plasmid-DNA design cycles, utilizing high content imaging of cellular phenotypes to guide the AI models. Designs serve to both probe pathways and modulate them - functioning as a unified platform for target discovery and lead development. Key innovations are propietary nucleotide level mRNA generative models, and a reinforcement learning design loop guided by cellular imaging. 

How GenScript LSRG Helps

The BLI assays performed at GenScript allow us to show that our in-silico protein design process is able to design binders at very high success probability. We can now use the results of this assay to guide our designs in the following cellular assays.

What We Do

Adeno-Associated Viruses (AAVs) are highly promising vectors for gene therapies due to their high efficiency, sustained expression, and low toxicity. However, robust delivery vehicles to the central nervous system (CNS) are lacking. My project aims to discover novel delivery mechanisms targeting diverse cell types within the CNS and explore how they respond to different transgenes. Over the past 25 years, the Schaffer lab has developed large AAV libraries through capsid diversification including error prone PCR, capsid shuffling, “loop swap”, and peptide display. Through directed evolution, I screened these libraries with clinically relevant human brain slices and non-human primates to identify CNS-specific AAV variants. Here, I propose to use next-generation sequencing (NGS) coupled with machine learning approaches to predict cell-specific, high infectivity AAV libraries. In summary, I aim to discover clinically relevant gene delivery approaches for various cell types within the CNS, ultimately treating complex neurological diseases, which currently have very limited therapies.

How GenScript LSRG Helps

GenScript award provides us a great opportunity to construct our AAV libraries and to explore the power of high-throughput DNA synthesis.

The flexibility of GenScript team and the fast turn-around time greatly benefit our project in moving forward with AAV screening and validating.

What We Do

Dr Kevin Sek is a cancer researcher and immunologist at the Peter MacCallum Cancer Centre under the supervision of Professor Phillip K. Darcy. Dr Sek’s research interest includes novel cell and gene-therapies for the treatment of cancer with a specific focus on adoptive CAR-T cell therapy for solid tumors. Utilizing gene and epigenome editing tools, as well as mRNA and Lipid Nanoparticle delivery platforms, he seeks to target fundamental T cell biology and the tumor microenvironment to enhance CAR-T cell therapies for various malignancies. He places a strong emphasis on translational research, with several pre-clinical adoptive therapies and drug pipelines in development for biotech companies Prescient and Myeloid Therapeutics.

How GenScript LSRG Helps

This LSRG grant provides me with the funding to kick-start a high-risk, high-reward research project that is at the forefront of cancer immunotherapy. GenScript’s high quality and rapid plasmid, mRNA and AAV services has drastically reduced the time it has taken to translate ideas into real-world feasibility data which will attract further funding and development.

What We Do

African swine fever (ASF) is a deadly transboundary disease that spreads through pigs, boars, and various fomites. When ASF is detected on a farm, the entire pig herd must be destroyed, and this has a devastating impact on the global pork industry. To date, there are three ASF vaccines at different stages of commercialization. Vaccines add incredible value to the industry and biosecurity programs worldwide, but there is a critical need to differentiate infected from vaccinated animals (DIVA), also known as a DIVA test. There are no commercial ASF DIVA tests, and therefore, current ASF diagnostics could produce a false positive result. Herein, we propose to develop technology for enzyme linked immunosorbent assays (ELISA) ASF DIVA tests against ASF-delta-MGF and ASF-delta-9GL/UK vaccines. Our project will employ GenScript’s peptide synthesis and protein production services to generate vaccine-specific antigens for ELISA development. We will collaborate with ASF research and diagnostics laboratories in our network to evaluate each ELISA. Our project is an important step towards providing the pork industry with ASF DIVA tests, which will impact the ability to manage disease and reduce the economic impacts of ASF.

How GenScript LSRG Helps

The LSRG-funded GenScript services will significantly reduce the cost of ELISA development for this project. By outsourcing peptide synthesis and protein production, we are saving valuable time and effort to focus on R&D.

What We Do

Cellular immunotherapy, particularly with T cells engineered to express chimeric antigen receptors (CAR-T cells), has shown significant promise in treating certain hematological malignancies. However, the need for effective therapies against other blood cancers and solid tumors remains critical. Our research focuses on developing a novel approach to cancer immunotherapy by genetically enhancing "adaptive" Natural Killer (NK) cells using CRISPR/Cas9 technology. Adaptive NK cells are a unique subset of NK cells found in a significant proportion of cytomegalovirus (CMV) positive individuals. These cells possess robust cytotoxic potential and a distinct receptor repertoire that enhances their ability to target and kill cancer cells. Our project aims to create an off-the-shelf NK cell therapy by editing three key aspects of these cells: enhancing cytotoxic potency, expanding the range of targetable cancer types, and extending cell persistence. By leveraging CRISPR/Cas9-mediated gene knock-outs and knock-ins, we intend to boost the natural properties of ADAPT-NK cells, ultimately advancing a powerful and versatile cell therapy platform for treating both hematological malignancies and solid tumors.

How GenScript LSRG Helps

The LSRG-funded GenScript services will significantly enhance our project by providing high-precision CRISPR/Cas9 gene editing tools and reagents, enabling us to execute multiple, targeted genetic modifications in adaptive NK cells with greater accuracy and efficiency. This will be crucial for developing a potent and scalable NK cell therapy for cancer treatment.

What We Do

Alzheimer's disease (AD) is the most common form of dementia and progressively affects memory, thinking and daily activities. AD has been long characterized with two hallmarks in the brain: neurofibrillary tangles in neurons and extracellular amyloid plaques, which are composed of hyperphosphorylated tau and amyloid beta respectively. There is mounting evidence for adaptive immune responses in people who have AD. However, the role of adaptive immunity in AD remains largely unknown. Our large cohort and multi ancestry GWAS have identified a protective effect of human leukocyte antigen (HLA)-DRB1*04 sub alleles, strongest with DRB1*04:04 and DRB1*04:07, intermediary with DRB1*04:01 and DRB1*04:03, and absent for DRB1*04:05. We found a particular piece of peptide from tau bound to DRB1*04:04 and DRB1*04:01 but not DRB1*04:05 only when it was modified by acetylation at lysine (K) 311, namely PHF6 aK311. We hypothesize that there are specific T cell immune responses to PHF6 aK311 presented by DRB1*04:04 . Our project is to characterize the role of these T cells in AD.

How GenScript LSRG Helps

The GenScript LSRG will help us synthesize overlapping peptides from tau and other antigens with high purity, including post-translational modifications (PTMs), and facilitate the isolation and characterization of antigen-specific T cells using multimer HLAs.