Lentivirus

The binding of Programmed Cell Death Protein 1 (PD-1), a receptor expressed on activated T-cells, to its ligands, PD-L1 and PD-L2, negatively regulates immune responses. PD-1 ligands are found on most cancers, and the PD-1:PD-L1/2 interaction inhibits T-cell activity and enables cancer cells to escape immune surveillance. The PD-1:PD-L1/2 pathway is also involved in regulating autoimmune responses, making these proteins promising therapeutic targets for a number of cancers, as well as multiple sclerosis, arthritis, lupus, and type I diabetes. The PD-1 CRISPR Lentiviruses are replication incompetent, HIV-based VSV-G pseudo-typed lentiviral particles that are ready to be transduced into almost all types of mammalian cells, including primary and non-dividing cells. The particles contain a CRISPR/Cas9 gene driven by an EF1a promoter, along with 4 sgRNA (single guide RNA) targeting human PD-1 (Programmed Cell Death 1, PDCD1, CD279, GenBank Accession #NM_005018) driven by a U6 promoter.

Lymphocyte-activation gene 3 (LAG3, CD223) is a cell surface protein that belongs to the immunoglobulin (Ig) superfamily. LAG3 is expressed on activated T-cells, Natural Killer cells, B-cells, and plasmacytoid dendritic cells. Its main ligand is the MHC class II, to which it binds with higher affinity than CD4. It negatively regulates cellular proliferation, activation, and homeostasis of T-cells in a similar fashion as CTLA-4 and PD-1, and has been reported to play a role in T-reg suppressive function. A number of LAG3 antibodies are in preclinical development for the treatment of cancer and autoimmune disorders. LAG3 may be a better immune checkpoint inhibitor target than CTLA-4 or PD-1, because antibodies targeting CTLA-4 or PD-1 only activate effector T-cells while failing to inhibit T-reg activity, whereas an antagonist LAG3 antibody can both activate effector T-cells (by downregulating the LAG3 inhibiting signal) and inhibit induced (i.e. antigen-specific) T-reg suppressive activ

CTLA4 (Cytotoxic T-Lymphocyte Associated Protein), also known as CD152, is a protein receptor that functions as an immune checkpoint. It is expressed by activated T-cells and transmits an inhibitory signal to T-cells. CTLA4 is homologous to the T-cell co-stimulatory protein CD28, and both molecules bind to CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells. CTLA4 binds CD80 and CD86 with greater affinity and avidity than CD28, thus enabling it to out-compete CD28 for its ligands and act as an "off" switch when bound to CD80 or CD86. CTLA4 is an important immunotherapy target for the treatment of cancer and autoimmune diseases. <br />The CTLA4 CRISPR Lentiviruses are replication incompetent, HIV-based VSV-G pseudo-typed lentiviral particles that are ready to be transduced into almost all types of mammalian cells, including primary and non-dividing cells. The particles contain a CRISPR/Cas9 gene driven by an EF1a promoter, along with 4 sgRNA (single guide RNA) targeting human CTLA4

The T-Cell Receptor (TCR) is found on the surface of T-cells and is responsible for recognizing antigens bound to MHC (Major Histocompatibility Complex) molecules. Activation of the TCR results in activation of downstream NFAT signaling. The TCR consists of a heterodimer of two different protein chains, of which the alpha (α) and beta (β) chains are the predominant chains. <br />The TCR CRISPR Lentiviruses are replication incompetent, HIV-based VSV-G pseudo-typed lentiviral particles that are ready to be transduced into almost all types of mammalian cells, including primary and non-dividing cells. The particles contain a CRISPR/Cas9 gene driven by an EF1a promoter, along with 4 sgRNA (single guide RNA) targeting human TRAC (T-Cell Receptor Alpha Constant) and human TRBC1 (T-Cell Receptor Beta Constant 1) regions of the α and β chains. <br />The non-integrating lentivirus is made with a mutated integrase, resulting in only transient expression of the Cas9 and sgRNA. Although using the

CD47 (also known as Rh-associated protein, GP42, Integrin-Associated Protein (IAP), or Neurophilin) is an immunoglobulin-like protein that interacts with its receptor, Signal-regulatory protein alpha (SIRPα), on macrophages. This binding interaction regulates transmigration, oxidative burst cytokine production, and phagocytosis, generating a "don't eat me"signal. CD47 is ubiquitously expressed on the surface of normal cells, but is overexpressed in numerous cancer cells where it is thought to contribute to the resistance of tumors to phagocyte-dependent clearance. The CD47 CRISPR Lentiviruses are replication incompetent, HIV-based VSV-G pseudo-typed lentiviral particles that are ready to be transduced into almost all types of mammalian cells, including primary and non-dividing cells. The particles contain a CRISPR/Cas9 gene driven by an EF1a promoter, along with 4 sgRNA (single guide RNA) targeting human CD47 (NM_198793.2) driven by a U6 promoter. <br />Note: unlike human CD47 CRISPR

The binding of Programmed Cell Death Protein 1 (PD-1), a receptor expressed on activated T-cells, to its ligands, PD-L1 and PD-L2, negatively regulates immune responses. The PD-1 ligands are found on most cancers, and the PD-1:PD-L1/2 interaction inhibits T-cell activity and allows cancer cells to escape immune surveillance. The PD-1:PD-L1/2 pathway is also involved in regulating autoimmune responses, making these proteins promising therapeutic targets for a number of cancers, as well as multiple sclerosis, arthritis, lupus, and type I diabetes. The PD-L1 CRISPR Lentiviruses are replication incompetent, HIV-based, VSV-G pseudo-typed lentiviral particles that are ready to be transduced into almost all types of mammalian cells, including primary and non-dividing cells. The particles contain a CRISPR/Cas9 gene driven by an EF1a promoter, along with 4 sgRNA (single guide RNA) targeting human PD-L1 (Programmed Cell Death 1 Ligand 1, CD274, B7 homolog 1 (B7-H1), GenBank accession #NM_021893

TIGIT (T-cell immunoreceptor with Ig and ITIM domains; VSTM3; VSIG9) is a co-inhibitory receptor that is highly expressed in Natural Killer (NK) cells and activated CD4+, CD8+, and regulatory T-cells. Interaction with the Poliovirus Receptor (PVR; CD155) on antigen presenting cells, such as dendritic cells, recruits either the Src homology (SH) domain-containing tyrosine phosphatases SHP1 and SHP2, or the Inositol phosphatase SHIP1 and SHIP2, to the TIGIT ITIM domain. This increases IL-10 release and suppresses NF-κB and NFAT T-cell receptor (TCR) signaling, which blocks T-cell proliferation and cytokine production. TIGIT also serves as a competitive inhibitor of CD226, a costimulatory receptor for CD155. TIGIT-targeting antibodies which block this T-cell intrinsic inhibitory effect have shown enhanced anti-tumor and anti-viral functions in preclinical studies. <br />The TIGIT CRISPR Lentiviruses are replication incompetent, HIV-based VSV-G pseudo-typed lentiviral particles that are r

Cas9 (Streptococcus pyogenes CRISPR associated protein 9) is an endonuclease enzyme that, when recruited to a specific DNA sequence by the sgRNA (single guide RNA), introduces a double stranded break into the DNA. This double stranded break is repaired in mammalian cells either through Non-Homologous End Joining or Homologous Recombination. Non-Homologous End Joining often results in the deletion or insertion of several base pairs at the cut site, which, when resulting in a frameshift, causes the functional inactivation of the targeted gene. <br />Cas9 Lentivirus can be used to generate Cas9 expressing cells in almost any mammalian cell line. Cells stably expressing Cas9 can then be transduced or electroporated with sgRNA targeting a gene of interest to quickly generate knock-out cell pools or cell lines. <br />The Cas9 Lentiviruses are replication incompetent, HIV-based VSV-G pseudo-typed lentiviral particles that are ready to be transduced into almost all types of mammalian cells,

Cas9 Lentivirus can be used to generate Cas9 expressing cells in almost any mammalian cell line. Cells stably expressing Cas9 can then be transduced or electroporated with sgRNA targeting a gene of interest to quickly generate knock-out cell pools or cell lines.<br /><br />The Cas9 Lentiviruses are replication incompetent, HIV-based VSV-G pseudo-typed lentiviral particles that are ready to be transduced into almost all types of mammalian cells, including primary and non-dividing cells. The particles contain a Cas9 gene driven by an EF1a promoter, along with a Hygromycin selection marker.