HOW DOES RALA WORK?

RALA can rapidly condense all nucleic acids (irrespective of size) and other anionic small molecules (such as chemotherapies, cyclic dinucleotides, nucleotides etc.) to form stable nanoparticles that readily cross cell membranes, escape endosomes to release the cargo with high transfection efficiency and low associated toxicity.

RALA Peptide : POSITIVE CHARGES

1/8

Drug Cargo : NEGATIVE CHARGES

(e.g. DNA, RNA, or Small Molecules)

SELF-ASSEMBLY OF ION PAIRS

Z-Average

< 100 nm

Forms Consistent & Stable Nanoparticles

Regardless of Cargo Type or Size

BENEFITS OF RALA

VERSATILE

High efficiency for condensing any nucleic acid or anionic small molecules into nanoparticles with industry acceptable characteristics

EFFICIENT

Cellular delivery of nucleic acids that outperforms current delivery platforms in vitro. RALA nanoparticles are capable of entering cells, disrupting endosomes, and releasing the cargo for maximal effect

RESISTANT

Physiologically stable nanoparticles with no protein binding, nanoparticle disassembly, or nanoparticle aggregation following exposure to physiological concentrations

SAFE

The natural amino acid composition ensures no toxicity even after multiple transfections in vitro or injections in vivo

THERAPEUTIC

RALA nanoparticles exhibit low immunogenicity. No vector neutralization or anti‐RALA antibodies are detected following repeated exposure in immune competent mice

STABLE

Highly stable formulations (>6 months) that are resistant to extremes of time and temperature, remaining intact and functional with no loss in transfection efficiency following lyophilisation

Mechanism Of Action

Ionic interactions between peptide and cargo allow nanoparticles to self-assemble with drug cargo making formulation simple, easy, and repeatable.

Positive (cationic) peptide with Negative (anionic) cargo

The ionic bond being formed with the cargo is typically both bidentate and bifurcated (two ionic interactions at a site with two or more sites forming bond).  This leads to extremely strong bonding and unsurpassed stability of RALA nanoparticles.

 

The net cationic nanoparticles now possess the ideal physiochemical characteristics and are readily taken up by cells, crossing the cell membrane with ease and being taken into cellular compartments known as endosomes.

 

The reduction in pH inside the endosome triggers a conformational change in the RALA peptide, enabling fusion with the endosomal membrane and subsequent proteolytic cleavage to release the cargo at the intended site of action.

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© 2020 by pHion Therapeutics Ltd.

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