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"Optimization of cell-penetrating peptides to enable therapeutics with intracellular targets"

Hanne Poulsen

Associate Professor

Department of Molecular Biology and Genetics & DANDRITE

Head of the P2P CPP project

 

M: hp@mbg.au.dk

T: +45 3025 4065

 

Aim

To increase the understanding of the physiological effects of cell-penetrating proteins (CPPs) and thereby eventually enable intracellular drug delivery using CPPs.

Approach

The P2P CPP team set up an iterative approach for testing CPP-drugs. First, the CPP-drug’s effects were analyzed in electrophysiological and vasodilation assays. Here, the P2P CPP team analyzed ion currents and arterial contractility in both rodents and humans. As a last step, the observed effects of the CPP-drugs were compared to the in vivo effect in mice.

Outcome

During the project (2021–2023), the P2P CPP team established an iterative framework for evaluating the safety and efficacy of cell-penetrating peptides (CPPs). The project generated new knowledge about the physiological effects of CPPs and provided a platform for selecting and optimizing CPPs for intracellular drug delivery, helping to accelerate the development of CPP-based therapeutics.

On this page, you can watch a video recorded at the beginning of the P2P CPP project. You can also read a very short cartoon introduction to the project or a longer article on the project outputs.

THE P2P CPP TEAM

Academic team members

  • Hanne Poulsen, Associate Professor, Aarhus University
  • Ulf Simonsen, Professor, Aarhus University
  • Daniel Otzen, Professor, Aarhus University
  • Xingya Chang
  • Estéfano Pinilla

Industrial team member

  • Richard Bethell, STipe Therapeutics

"It has been extremely inspiring and rewarding to work closely with STipe Therapeutics, especially with their CDO Richard. Richard has a really broad knowledge of drug development, and he has an incredible knowledge within chemistry and molecular biology. Therefore, he has quickly understood our results and helped us with interpretation and suggestions for substantiation.

It has been quite obvious to do the P2P CPP project as an open collaboration, since STipe Therapeutics' interest is in the specific mechanism of action of their active compounds and target - not the technical aspects of how these compounds achieve it. Our basic scientific curiosity, on the other hand, is in the wondrous molecular and physiological mechanisms of cell-penetrating peptides."

 

Hanne Poulsen, Head of the P2P CPP project

“Two pharma companies contacted us during the project. I guess they had heard about our project through the ODIN network because it’s a requirement that all findings are shared openly with the public. Most pharma companies are obviously interested in reaching some of the many potential intracellular targets, and we are happy to share our findings with them and anybody else, who are interested.”

 

Hanne Poulsen, Head of the P2P CPP project

ARTICLE

Read the article on the P2P CPP project to find out what the team learned about CPPs

"I’d like to be part of an ODIN project again because it was a fun and interesting experience to interact with collaborators in completely different fields of science. We learned and gained new perspectives on the mechanisms underlying the toxic effects of cell-penetrating peptides. Moreover, these techniques and approaches could be applied in our other projects."

 

Ulf Simonsen, Participant in the P2P CPP project

"As a company aiming to deliver peptides and other pharmacologically active molecules into cells to target intracellular proteins, and having seen unexpected toxicity in an early prototype molecule incorporating a cell-penetrating peptide (CPP), we had an interest in understanding the parameters that determine both the safety and efficacy of bioactive molecules that incorporate CPPs. It thus seemed an obvious project for the ODIN platform, and it was very gratifying to see the enthusiasm with which these questions were taken on by a diverse teams of excellent scientists. The group now has a novel hypothesis for a cause of the toxicity, which may enable the future optimization of this drug delivery technology."

 

Richard C Bethell, STipe Therapeutics

Industry partner in the P2P CPP project

ABOUT ODIN

We unite bright minds from industry and academia to jointly create need-driven clinical research projects - and pave the way for innovative new treatments and diagnostics. We fund the best project ideas through competitive funding calls. Although companies cannot receive funding, it is free of charge to join.

The platform is sponsored by the Novo Nordisk Foundation with 180 million DKK from 2024-2029.

CONTACT ODIN

You are welcome to contact us if you have questions or comments. Reach out to odin@au.dk or find the Secretariat's direct email addresses under contacts.

Although the platform spans five Danish universities, we're based in Aarhus. Our office is located at Aarhus University, Ny Munkegade 116, Bldg 1535-117.

Revised 02.07.2026
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Chantelle Dana Driever