Science

 

Conformational Diseases

Protein folding issues underlie many diseases, such as amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. These diseases are called “Conformational Diseases” because they are caused by protein folding problems (conformational problems). Elimination of the abnormally folded proteins from patients can be a silver bullet for these diseases. One of the major challenges is how to selectively reduce the abnormally folded proteins.

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JUMP70 Platform Technology

SOLA has developed an innovative “JUMP70” technology, to activate the patients’ own protein folding system specifically to “Disease-causing Protein”. We have demonstrated that JUMP70 Technology is effective to selectively eliminate misfolded Disease-causing Protein by the following mechanism of action.

Adeno-Associated Virus (AAV) vector is administered into a patient body

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Adeno-Associate Virus (AAV) encoding the JUMP70 gene is administered into a patient body. Administered AAVs will reach a disease area, such as nerve cells.

AAV vector carrying JUMP70 gene is introduced into disease target cells such as motor neuron cells and JUMP70 protein is produced intracellularly

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AAV vector with JUMP70 gene is internalized into the patient’s cell (e.g. neurons). Once AAV enters, AAV starts to synthesize JUMP70 proteins in the cells. AAV stays in the cells for a long time, leading to the long-lasting expression of JUMP70 proteins.

JUMP70 Protein attaches specific Disease-causing Misfolded Protein

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In a patient, “Disease-causing Misfolded Protein” is the culprit for the disease. Synthesized JUMP70 proteins capture Disease-causing Misfolded Protein” using Targeting domain. JUMP70 is designed not to capture “Functional properly-folded protein”.

Protein Folding Activation Domain associated with Disease-causing Protein is selectively recognized by Hsp70 Protein Folding system

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“Protein Folding Activation Doman” brings the patient’s protein folding system called Hsp70 to the captured “Disease-causing Misfolded Protein”.

Hsp70 Protein Folding system repairs or degrades the Disease-causing Protein selectively and the JUMP70 Protein will be recycled

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“Protein Folding Activation Domain” activates Hsp70 specifically for the captured “Disease-causing Misfolded Protein”. After the step, JUMP70 is released, and now free to engage another “Disease-causing Misfolded Protein”. “Disease-causing Misfolded Protein” will be properly folded through the cycle. If the protein folding is refractory and cannot be repaired, Hsp70 protein folding system sends the misfolded proteins to a cellular degradation system.

JUMP70 Technology Platform - Advantages

  • New Modality:
    • Engages the Hsp70 machinery to fix the protein misfolding problems
    • Exclusively and specifically engages misfolded proteins
    • Does not affect properly folded proteins
  • Adaptable: Readily adapted to virtually any intracellular target
  • Potent: Acts catalytically, rather than stoichiometrically
  • Highly specific: Two levels of specificity:
    1. Targeting Domain confers binding specificity
    2. Hsp70 system engages only misfolded proteins
  • Potential Refolding activity: Some misfolded proteins can be refolded, and may allow restoration of its intrinsic activity
  • Works on all cell types: Hsp70 is abundantly present in all human cell types
  • Suitable for gene therapy: JUMP70 proteins are easily adopted for gene therapy owing to its small size

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