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Laboratory work for GET-IN doctoral network

Doctoral Candidate 9

Central nervous system-targeted genome editing through engineered extracellular vesicles

PROJECT INFORMATION

Host institution of GET-IN Alia Therapeutics

Host institution: Alia Therapeutics, Italy

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Supervisory team: Dr. Antonio Casini (PhD promoter, Alia Therapeutics), Prof. Anna Cereseto (Università degli Studi di Trento), Prof. Rik Gijsbers (KU Leuven)

PROJECT DESCRIPTION 

This project aims at developing novel modalities and delivery strategies for CRISPR-based gene therapies. The objectives are: 1) To identify novel pseudotypes to be used in combination with VesiCas to target cells in the central nervous system (CNS); 2) To develop a cell-based screening system to allow the streamlined identification of potential candidates with the desired tropism characteristics to target the CNS; 3) To improve the VesiCas production process by engineering the currently used producer cell line and by optimization of the downstream purification processes (through mass spectrometry, next-generation sequencing, microscopy analyses).

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A successful project will result in: 1) A VesiCas-based platform to allow the tissue/cell-specific delivery of different genome editing tools to neuronal cell populations in vitro and in vivo; 2) Demonstration of VesiCas cargo flexibility by incorporating different genome editors (base editors, prime editors, epigenome editors) as well as novel CRISPR nucleases; 3) Validation of the best identified pseudotypes and novel cargo proteins in a relevant CNS disease model in vitro including preliminary in vitro immunogenicity tests; 4) Optimization of the VesiCas producer cell line and purification protocols to increase the overall yields. 

 

Enrolment in Doctoral School: Università degli Studi di Trento

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Planned secondments:

  • INSERM, France (Months 23-24): Introduction to nanoblades and comparison with VesiCas 

  • KU Leuven, Belgium (Months 31-32): Vector production and purification from optimised cell lines

ESSENTIAL REQUIREMENTS

  • You hold a master’s degree in Biology, bioscience engineering, biotechnology or a related field.

  • You are ambitious, well organized and have excellent communication skills.

  • You are proficient in English both spoken and written.

  • You have the ability to work independently and have a critical mindset.

  • You are an enthusiastic and motivated person, eager to participate in network wide training events, international travel and public awareness activities.

  • Willingness to travel.

SKILLS AND EXPERTISE 

  • Solid knowledge of CRISPR-Cas system and its uses in gene editing

  • An understanding of the biology of extracellular vesicles​

  • Basic knowledge of the processes behind extracellular vesicle production and purification

  • Basic knowledge on viral vectors, particularly lenti/retroviral vectors and AAVs

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