Modular Multifunctional Protein Vectors for Gene Therapy

Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy

“…This suggests engineering the HNRK vector can be further improved using other known endosome escaping motifs. 18 Alternatively, chloroquine could be co-injected with assembled nanovector in vivo to increase transfection efficiency, as chloroquine has been approved for use in human subjects. Finally, instead of performing an intracerebral injection, protein nanovectors could be administered by an intravenous route and may reach the brain after TBI where the blood–brain barrier has been altered.…”

“… 13–15 Nonintegrating lentiviral vectors, in particular, show promising features for use in treating CNS disorders. 16 , 17 Nonviral vectors have also gained attention, 6 , 7 , 10 , 18 and in particular, vehicles based on multifunctional proteins in DNA complexes. These vectors constitute a very versatile type of carrier for therapeutic nucleic acids, constructed by combining appropriate functional domains fused as a single polypeptide chain.…”

“… 6 , 10 The modular nature of such constructs allows for selection and incorporation of well-characterized peptides with different features so as to improve function by iteratively redesigning the construct. 18 , 20 Several nanovectors of this type can be successfully used to transfect cells in vitro 10 , 21–25 and to result in the expected therapeutic effect when used in vivo . 26–29 There is thus great interest in developing the potential of these nanovectors for use in a clinical context.…”

CSSI workshop in Brazil highlights “Stress Responses in the Nervous System” in relation to neurodegenerative diseases and neuroprotection

“…Classical anti-inflammatory drugs have failed in the limitation of this secondary pro-inflammatory damage, but cell-based strategies aimed to modulate this process show interesting potential (Peluffo et al 2006(Peluffo et al , 2007. One of these strategies is gene therapy (Domingo-Espin et al 2011;Peluffo 2011), which has recently shown important success in long-term clinical settings for CNS pathologies such as Parkinson's disease (Broadstock and Yanez-Munoz 2012).…”