TS-005768 — This novel genetic construct for allogeneic cellular therapies enables immune‑evasive persistence by selectively downregulating HLA class I molecules while preserving natural killer (NK) cell inhibition.

TS-005689 —

TS-005674 — This IP is a novel RNA‑targeted therapeutic strategy for alveolar rhabdomyosarcoma (ARMS) using CRISPR‑Cas13d to enable the highly specific degradation of the oncogenic mRNA while preserving the wild‑type PAX7 and FOXO1 genes, avoiding the genotoxicity risks associated with DNA‑targeting CRISPR systems.

TS-004607 — Using CRISPR/Cas9 genome editing can eliminate an inhibitory checkpoint receptor called TIGIT, which improves anti-tumor activity and cellular therapy for cancer. Chimeric antigen receptor technology also introduces an immune activating CAR within the TIGIT gene locus.

TS-003705 — This IP solution aims to enhance the efficacy of Natural Killer (NK) cell therapy in cancer immunotherapy. By targeting the ADAM17 gene using CRISPR technology, it intends to maintain the expression of CD16 on NK cells, crucial for antibody-directed cell cytotoxicity (ADCC) against tumor cells. Cryopreserved ADAM17 knockout (KO) NK cells demonstrated significantly higher CD16 expression post-thaw, leading to enhanced ADCC against cancer cell lines when combined with antibodies. This advancement addresses a critical issue in cancer immunotherapy and ensures sustained antitumor activity of NK cells even after cryopreservation. It holds potential applications in various off-the-shelf adaptive NK cell products, catering to a wide range of cancer types and patient needs. Companies in cellular immunotherapy may find this IP valuable for developing next-generation NK cell therapies with improved efficacy and versatility. With further development and testing planned—including evaluation in in vivo models and expansion using different cytokines—the IP presents a promising avenue for advancing cancer treatment strategies.

TS-003693 — CD34+ Bone Marrow Stem Cells for the Treatment of Chronic Granulomatous Disease (CGD) Chronic Granulomatous Disease (CGD) is a genetic disorder characterized by defective immune cells unable to produce Reactive Oxygen Species (ROS); this compromises someone’s ability to fight infections. Current treatments, such as antimicrobial prophylaxis, only partially address the condition. This IP proposes a novel approach utilizing CRISPR/AAV technology to genetically edit autologous CD34+ bone marrow stem cells ex-vivo, aiming to restore the normal function of immune cells and improve clinical outcomes for CGD patients. The technology involves off-the-shelf CRISPR guide RNAs (gRNAs) targeting mutated genes in CGD, along with adeno-associated virus (AAV) vectors delivering healthy copies of these genes. This technology offers a promising solution to the limitations of existing CGD treatments by addressing the root cause of the disease at the genetic level. By genetically editing autologous CD34+ stem cells ex-vivo, the technology seeks to produce functional immune cells capable of effectively combating infections in CGD patients. This approach has the potential to significantly improve the quality of life and life expectancy of CGD patients, offering a new avenue for personalized medicine in the treatment of genetic disorders. Compared to conventional treatments (e.g., antimicrobial prophylaxis) this gene therapy approach offers the advantage of directly addressing the underlying genetic defect in CGD. By utilizing CRISPR/AAV technology, the off-the-shelf materials provided can efficiently target and replace mutated genes in CD34+ stem cells, potentially resulting in a higher percentage of ROS production and improved immune function. Further development of this technology involves generating corrected CD34+ stem cells targeting the CYBB, CYBA, NCF1, and NCF2 genes associated with CGD mutations. These corrected cells will be tested in preclinical models to assess their antimicrobial activity and therapeutic efficacy. Ongoing research will focus on optimizing the gene editing process and expanding the application of the technology to other genetic disorders beyond CGD. Pharmaceutical companies specializing in gene therapy, immunology, and rare diseases are likely to be interested in licensing this technology for further development and commercialization.

TS-003689 — This IP exhibits a significant advancement in cancer immunotherapy. It encompasses a novel scFv designed to specifically target CD33, a surface antigen commonly expressed in hematologic cancers such as leukemia, myeloma, and lymphoma. This scFv serves as a fundamental component in various therapeutic modalities, such as chimeric antigen receptor (CAR) T-cell and natural killer (NK) cell therapies. Hematologic cancers pose significant challenges in treatment and often require targeted therapeutic approaches. The scFv targeting CD33 offers a promising solution by enabling the development of highly specific immunotherapies. CAR-T cells and CAR-NK cells engineered with this scFv can selectively recognize and eliminate CD33-expressing cancer cells while sparing healthy tissues, thus potentially improving treatment efficacy and minimizing adverse effects associated with traditional therapies. The IP’s innovative design features an alternative linker and an unexpected reverse orientation of the variable heavy (VH) and variable light (VL) chains, potentially conferring advantages in terms of binding affinity and epitope recognition. This enhances the specificity and effectiveness of CD33-targeted therapies, offering improved treatment outcomes for patients. The applications of the scFv targeting CD33 are extensive and includes both immediate and future uses. In the short term, it can be incorporated into CAR-T cell and CAR-NK cell therapies for the treatment of CD33-positive hematologic cancers. Additionally, the scFv may find utility in the development of other CD33-targeted therapies—including bispecific antibodies and antibody-drug conjugates—expanding its therapeutic potential across a broader range of malignancies. Biopharmaceutical companies involved in cancer immunotherapy may express interest in licensing this innovative technology. Further development of the scFv targeting CD33 involves in vivo assays to evaluate its efficacy against human hematologic cancer xenografts in animal models. Ongoing research efforts will focus on optimizing the scFv sequence and engineering CAR-T and CAR-NK cells expressing this scFv for preclinical and clinical studies. These endeavors aim to establish proof of concept and advance the technology towards eventual clinical translation.

TS-003681 — The IP revolves around the development of CD70 knockout natural killer (NK) cells and their integration with CD70 chimeric antigen receptor (CAR) technology to overcome fratricide—a phenomenon where CAR-expressing NK cells attack each other. This method employs gene editing techniques like CRISPR and AAV to target the CD70 gene and integrate CAR constructs into the CD70 locus of NK cells. The IP aims to enhance the effectiveness of CAR-NK cell therapy, particularly in the context of CD70-positive tumors. By eliminating CD70 expression in NK cells and simultaneously integrating CAR constructs into the CD70 locus, it mitigates fratricide, thereby enhancing the survival and functionality of engineered NK cells in the tumor microenvironment. Unlike existing methods, which may suffer from fratricide when CAR-NK cells target antigens present on their own surface, the IP offers a unique solution by leveraging the CD70 gene as an integration site for CARs. This strategy not only overcomes fratricide but also enhances the specificity and potency of CAR-NK cells, potentially leading to improved therapeutic outcomes. The IP holds promise for various cancer types, including glioblastoma, T cell lymphomas, and B cell malignancies, where CD70 expression is prevalent. Additionally, the modular nature of CAR-NK cells allows for customization to target different antigens, broadening its application across diverse malignancies. The market for personalized cancer treatments continues to grow, making this technology highly attractive for commercialization. The IP has demonstrated successful generation and functionality of CD70 knockout/CD70 CAR-NK cells, progressing from conceptualization to proof of concept. Further development involves characterization and optimization of these engineered NK cells for clinical translation.

TS-003676 — The IP introduces a novel methodology aimed at tackling autosomal dominant genetic disorders. By harnessing the power of CRISPR technology and guided RNA (gRNA) design, this IP offers a targeted approach to address mutant alleles while preserving the expression of healthy alleles. It can precisely target mutant alleles associated with autosomal dominant disorders, paving the way for potential therapeutic interventions. Unlike conventional approaches, this methodology leverages specific gRNA design, incorporating mutated sequences adjacent to the protospacer adjacent motif (PAM) sequence. This allows for the selective targeting of mutant alleles and minimizes off-target effects and preserving the expression of healthy alleles. At its current stage, proof-of-concept experiments have demonstrated the efficacy of gRNAs targeting mutant alleles associated with specific disorders. Future development efforts will focus on expanding the scope of application to other autosomal dominant genetic disorders and refining the methodology for clinical translation. Its tailored approach to gRNA design offers enhanced precision and specificity, reducing the risk of unintended genetic modifications. The IP has broad utility and commercial potential; the versatility of CRISPR technology allows for its potential application in a wide range of autosomal dominant disorders beyond the initial target.

TS-003673 — The IP focuses on pairing oncolytic viruses with engineered adoptive cell therapies, such as CAR-T and CAR-NK cells, to enhance their anti-tumor capabilities within challenging tumor microenvironments. The significance of this IP lies in its ability to address several key challenges in cancer immunotherapy. By engineering the oncolytic virus to express T cell activating cytokines and modifying T or NK cells to interrupt inhibitory pathways while inserting genes regulated by virus-expressed factors, this approach aims to improve the safety and efficacy of engineered cell therapies. Additionally, the use of SynNotch technology for regulated gene expression is a novel strategy for enhancing therapeutic specificity and activity. The stage of development for this IP is currently at the conceptual and prototype phase, with further work planned for validation and refinement. The IP offers compelling advantages over existing methods. Its safety, specificity, and activity (coupled with the ability to regulate cell function using oncolytic viruses) appeal to biotechnology and pharmaceutical companies seeking innovative cancer therapies. The potential applications of this technology extend beyond CAR expression, paving the way for future developments in targeted cancer immunotherapy and gene regulation.