Gene Therapy of Renal Diseases and Study of N-terminal Acetylation of Proteins

"We have identified small molecules capable of inhibiting the NatB enzyme and that could be the basis of a new antitumor and antimetastatic therapy."

DR. RAFAEL ALDABE ARREGUI
RESEARCHER. GENE THERAPY OF RENAL DISEASES AND STUDY OF N-TERMINAL ACETYLATION OF PROTEINS RESEARCH GROUP

The Gene Therapy of Renal Diseases and Study of N-terminal Acetylation of Proteins Group focuses its research in two lines:

 

  • N-terminal acetylation of proteins: molecular study of protein deregulation processes and pathologies associated with these processes. Our group has proved that the activity of the amino-terminal acetyltransferase NatB acetylates the initial methionine whenever it precedes any of these 4 amino acids: Glu, Asp, Asn, Gln. The NatB enzyme is essential for the actin cytoskeleton to organize and function properly. Its inhibition blocks cell motility by affecting the function of one of its substrates: tropomyosin. In turn, we have observed its relationship with hepatocarcinoma, identifying small molecules capable of inhibiting NatB, with which to develop antitumor and antimetastatic therapies.
  • Renal gene therapy: a large number of renal diseases are caused by deficiencies or mutations in a single gene (monogenic). The challenge lies in transporting the genetic material to the different cells of the kidney. The best transporters available are those based on viral vectors based on adeno-associated viruses (AAV) that have demonstrated their efficacy in reaching the kidney through appropriate routes of administration and delivery systems.

 

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Objectives of our research

N-terminal acetylation of proteins

  • Identify and characterize biological functions and pathologies regulated by the NatB enzyme.
  • To identify NatB enzyme substrates whose biological activity is associated with its amino-terminal acetylation.
  • To develop new therapeutic treatments based on the regulation of the activity of this enzyme or its interaction with some of its substrates.

Renal gene therapy

  • To develop gene therapy vectors based on adeno-associated viruses (AAV) capable of transducing different renal cell types. 
  • To study the effect of binding different molecules to AAV capsid proteins to vary their tropism.
  • To evaluate the potential of AAVs to develop treatments for monogenic renal diseases.

Scientific activity of the Gene Therapy of Renal Diseases and N-terminal Protein Acetylation Research Group