Direct in vivo delivery agent

To assist in the directed delivery of siRNA molecules into animals, BIOO offers antibodies conjugated to protamine sulfate. Protamine sulfate is a small, positively charged, arginine rich protein which is traditionally used to reverse the anticoagulant effects of heparin by binding to it. It has been found that protamine sulfate can also associate with nucleic acids such as siRNA and miRNA molecules. For this reason protamine sulfate conjugated antibodies have significant potential to be used with RNAi agents for the directed delivery of these agents into animal tissues via cell surface receptors.

To generate RNAi agent bound to protamine sulfate conjugated antibody, simply mix the RNAi agent with the conjugated antibody in the antibody storage buffer and incubate at 30°C for 15 minutes. Following the incubation the RNA/antibody complex can be diluted into a sterile saline solution and injected directly into the animal.

*Custom antibody-protamine conjugates are available upon request*

If the antibody you are interested in evaluating for directed in vivo delivery is not listed we can generate monoclonal antibody against the target of interest in 5 weeks provided that the antigen is supplied to us.

CD4 V1 Ab Conjugated to Protamine, ref 3604

CD4 is a glycoprotein that is expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages and dendritic cells. CD4, together with the T cell receptor, recognizes MHC class II molecules. CD4 cell counts are used as indicator of AIDS progression. In addition to virus binding, CD4 may have an active role in membrane fusion.

References: Healey D et al. 1990. J. Exp. Med. 172(4):1233-1242.

Dornan S et al. 2002. J. Biol. Chem. 277(3):1912-8.

CD33 Ab Conjugated to Protamine, ref 3602

CD33 is expressed by monocytic/myeloid lineage cells including most acute myloid leukemias. CD33 is an adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. It preferentially binds to alpha2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, it may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. CD33 induces apoptosis in acute myeloid leukemia (in vitro).

Her2 Ab Conjugated to Protamine, ref 3601

The erbB family of receptor tyrosine kinase proteins includes epidermal growth factor receptor (EGFR), HER2 (erbB2), HER3 (erbB3) and HER4 (erbB4). These cell membrane receptors are composed of an extracellular ligand-binding domain, a transmembrane lipophilic domain, and an intracellular tyrosine kinase domain. Phosphorylation of the tyrosine kinase domain followed by homodimerization between different receptors of the same family leads to protein activation that promotes signaling cascades including ERK1/2 that promote cell growth. All but HER2 bind to receptor-specific ligands; however, under conditions of over-expression or mutations HER2 can become constitutively activated. EGFR and HER2 are highly expressed in many tumor types of epithelial origin, including breast, head and neck, bladder cancers and non-small cell lung cancer. The expression of high levels of EGFR and HER2 is associated with poor prognosis. Several anticancer drugs targeting EGFR family members have been developed and are often successful at treating disease.

Antibody mediated uptake into SKBR3 (HER2 positive) cells using Cy3 siRNA with the HER2 antibody protamine conjugate.

VEGFR2 (KDR) Ab Conjugated Protamine, ref 3603

The vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) pathway regulates proliferation, survival, and permeability of vasculature. One important pathway regulating angiogenic events is VEGF acting through two receptors: VEGF receptor 1 (VEGFR-1) and VEGFR-2. It is thought that VEGF-dependent activation of VEGFR-2 is involved in mediating endothelial cell proliferation, survival, and vascular permeability, whereas VEGFR-1 might play an inhibitory role by sequestering VEGF, and thus preventing its interaction with VEGFR-2. The VEGF/VEGFR-2 pathway is active in angiogenesis, as evidenced by the fact that substances inactivating VEGF or the VEGFR-2 interfere with blood vessel proliferation.

 

Reference	Description	Qté	Prix unitaire Euros HT
3601	Her2 Antibody Conjugated to Protamine	2mg	sur demande
3602	CD33 Antibody Conjugated to Protamine	2 mg	sur demande
3603	VEGFR2 (KDR) Antibody Conjugated to Protamine	2 mg	sur demande
3604	CD4 V1 Domain antibody conjugated to Protamine	2 mg	sur demande