Composite

Part:BBa_K4482012

Designed by: Matteo Da Ros   Group: iGEM22_NYC_Empire_State   (2022-09-30)


HIRMAb-HC-NT3

The insulin receptor is a transmembrane protein expressed in many different tissues in the human body, including endothelial cells forming the blood vessels in the brain. The insulin receptor takes an active part in transporting insulin from the blood stream into the brain through the blood bran barrier (BBB). This property of the insulin receptor has been harnessed to for the active transport of therapeutic proteins through the BBB. The human insulin receptor monoclonal antibody (HIRMAb) was developed to hitchhike into the insulin receptor and be transported through the BBB to deliver cargoes into the brain when injected intravenously. Antibodies are immunoglobulins formed by two different peptides, a heavy chain and a light chain, that complex together in couples to form the mature antibody capable of recognizing its specific antigen. This part represents the coding sequence for the heavy chain of the HIRMAb recombinant antibody. The sequence was derived from the protein sequence registered in US patent US-8858950-B2. Neurotrophin-3 is a protein that in humans is encoded by the NTF3 gene. The protein encoded by this gene, NT-3, is a neurotrophic factor in the NGF (Nerve Growth Factor) family of neurotrophins. It is a protein growth factor which has activity on certain neurons of the peripheral and central nervous system; it helps to support the survival and differentiation of existing neurons, and encourages the growth and differentiation of new neurons and synapses. NT-3 was the third neurotrophic factor to be characterized, after nerve growth factor (NGF) and BDNF (Brain Derived Neurotrophic Factor). Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain retain the ability to grow new neurons from neural stem cells; a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis. NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB). NT-3 is unique in the number of neurons it can potentially stimulate, given its ability to activate two of the receptor tyrosine kinase neurotrophin receptors (TrkC and TrkB. (Source: wikipedia). NT-3 was fused to the C-terminus of HIRMAb-HC so that it could be transported from the blood stream through the BBB into the brain.


Sequence and Features


Assembly Compatibility:
  • 10
    INCOMPATIBLE WITH RFC[10]
    Illegal EcoRI site found at 1917
    Illegal EcoRI site found at 2010
    Illegal XbaI site found at 1771
    Illegal SpeI site found at 262
    Illegal SpeI site found at 2026
    Illegal PstI site found at 1354
  • 12
    INCOMPATIBLE WITH RFC[12]
    Illegal EcoRI site found at 1917
    Illegal EcoRI site found at 2010
    Illegal SpeI site found at 262
    Illegal SpeI site found at 2026
    Illegal PstI site found at 1354
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal EcoRI site found at 1917
    Illegal EcoRI site found at 2010
    Illegal BamHI site found at 1415
    Illegal XhoI site found at 16
  • 23
    INCOMPATIBLE WITH RFC[23]
    Illegal EcoRI site found at 1917
    Illegal EcoRI site found at 2010
    Illegal XbaI site found at 1771
    Illegal SpeI site found at 262
    Illegal SpeI site found at 2026
    Illegal PstI site found at 1354
  • 25
    INCOMPATIBLE WITH RFC[25]
    Illegal EcoRI site found at 1917
    Illegal EcoRI site found at 2010
    Illegal XbaI site found at 1771
    Illegal SpeI site found at 262
    Illegal SpeI site found at 2026
    Illegal PstI site found at 1354
  • 1000
    INCOMPATIBLE WITH RFC[1000]
    Illegal BsaI site found at 1077
    Illegal BsaI.rc site found at 39
    Illegal SapI.rc site found at 387


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Parameters
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