TransMTS™ - Macromolecule Transport Technology

Description

The Revance TransMTS™ technology enables transcutaneous delivery of large macromolecules, eliminating the need for injections or other invasive procedures.

The TransMTS proprietary peptide is a single, straight-chain, peptide which has two distinct types of domains:

• The core of the peptide is a sequence of consecutive lysines, each of which confers a positive charge to the peptide. The purpose of this positively charged domain is to form a noncovalent bond with the negatively charged surface of the protein to be transported. Revance's lead product using the transport technology is a proprietary botulinum toxin type A molecule.

• The second type of domain is a Protein Transduction Domain (PTD) which is responsible for transcutaneous flux. There are two identical PTDs at each end of the peptide sequence. These PTDs are derived from residues of the transactivator of transcription (TAT) protein.

The positively charged core of the Revance TransMTS peptide forms a noncovalent bond with our proprietary botulinum toxin type A molecule while the PTD sequences facilitate its delivery.

Mechanism of Action

The TransMTS technology utilizes two complementary pathways, both of which are present in human skin.

The first pathway is energy independent and therefore can occur in non living cells (like the stratum corneum) as well as living cells in the skin.

This pathway allows the molecule to bind and traverse the stratum corneum via lipid rafting where the molecule "shuttles" across the surface of the lipid layers.

The second pathway is energy dependent and occurs across living cells.

• It is a transcytosis "shuttle" that actively takes the molecule from one side of the cell to another.
• The TransMTS technology triggers the cell to fold around the peptide taking the target molecule with it. 
• The depth of penetration is determined by the structure of the peptide. The TransMTS technology can deliver target molecules either superficially of deeper depending on the therapeutic need. The TransMTS technology has broad applicability and proof of concept work has been done across a variety of classes – including insulin, antibody derived therapeutics, growth factors, non-steroidal anti-inflammatory drugs and botulinum toxin type A.

Video: TransMTS Mechanism of Action

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