Stabilizing lipids

Abstract

The present invention generally relates to the field of lipids, in particular stabilizing lipids, and in particular provides a novel type of such lipids as represented by any of the formula disclosed herein. The present invention further provides methods for making such lipids as well as uses thereof, in particular in the preparation of nanoparticle compositions, more in particular nanoparticle compositions comprising active agents. It further provides pharmaceutical formulations comprising nanoparticle compositions based on the stabilizing lipids disclosed herein.

Description

[0001] STABILIZING LIPIDS FIELD OF THE INVENTION The present invention generally relates to the field of lipids, in particular stabilizing lipids, and in 5 particular provides a novel type of such lipids as represented by any of the formula disclosed herein. The present invention further provides methods for making such lipids as well as uses thereof, in particular in the preparation of nanoparticle compositions, more in particular nanoparticle compositions comprising active agents. It further provides pharmaceutical formulations comprising nanoparticle compositions based on the stabilizing lipids disclosed 10 herein. BACKGROUND TO THE INVENTION Nanoparticles, such as liposomes and lipid nanoparticles are increasingly being used in 15 therapeutic areas for the delivery of active agents, such as small molecules, proteins, nucleic acids, etc. to cells. One of the main requirements for medical use of nanoparticles is that they need to combine efficient and stable encapsulation of the active agents upon storage and in the extracellular environment, with maximum cellular uptake and efficient release of their payload into the cells. 20 Lipid nanoparticles comprising combinations of cationic lipids with other lipid components have been used to facilitate such cellular uptake of active agents. For example, lipid-based nanoparticles are typically composed of a cationic or ionizable lipid that can be protonated at acid pH, a helper lipid (e.g. phospholipid), a stabilizing lipid (e.g. PEGylated lipid) and a sterol, 25 and have been used in the delivery of nucleic acids. Each component of a nanoparticle has specialized functions in stability and activity of the nanoparticles. Therefore, further improvements in stabilizing lipid chemistries are needed to improve efficacy and safety of nanoparticle delivered active agents. 30 Accordingly, the present invention relates to a new class of stabilizing lipids as defined by the present set of claims, which have improved characteristics over the currently available classes of stabilizing lipids. -2- SUMMARY OF THE INVENTION In a first aspect, the present invention provides a stabilizing lipid represented by formula (I) 5 wherein n is an integer from 2 to 100; m is 0, or an integer selected from 1 to 100; R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more 10 heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each 15 of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; 20 each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further 25 comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally -3- and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; 5 Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising 10 one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. In an embodiment, the present invention provides a stabilizing lipid as defined herein, and represented by formula (I) 15 wherein n is an integer from 2 to 100; m is 0; 20 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from -C(O)NR2-, -OC(O)NR2-, and -C(O)O-; 25 R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently -4- substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; 5 X and X’ are each independently selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, and -C1-12alkylene-; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally 10 and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, and -SH; Z is selected from -Ph, -Bn, and -S-C1-12alkyl; 15 Y2 is selected from -H, -CN, and -Ph; and Y2’ is selected from -H, and -C1-6alkyl. In a further embodiment, the present invention provides a stabilizing lipid as defined herein, and represented by formula (II) 20 wherein n is an integer from 2 to 100; m is 0, or an integer selected from 1 to 100; 25 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted -5- with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently 5 substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; 10 each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl 15 and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; 20 Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising 25 one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl.

[0002] -6- In a further embodiment, the present invention provides a stabilizing lipid as defined herein, and represented by formula (III) 5 wherein n is an integer from 2 to 100; m is 0, or an integer selected from 1 to 100; R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more 10 heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently 15 substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; 20 each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl 25 and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - -7- O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; 5 Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. 10 In a further embodiment, the present invention provides a stabilizing lipid as defined herein, and represented by formula (IV) 15 wherein n is an integer from 2 to 100; R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted 20 with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises 25 one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; -8- the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X is selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; 5 L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally 10 and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; 15 Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently 20 substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. In a further embodiment, the present invention provides a stabilizing lipid as defined herein, and represented by formula (V) 25 wherein n is an integer from 2 to 100; -9- R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; 5 R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; 10 the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X is selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein 15 each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is20 optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; 25 Y2’ is selected from -H, and -C1-6alkyl; R2’is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. 30 In a further embodiment, the present invention provides a stabilizing lipid as defined herein, wherein Y2 is -CN, and Y2’ is -CH3; or wherein Y2 is -H, and Y2’ is -CH3. In a further embodiment, the present invention provides a stabilizing lipid as defined herein, 35 wherein n is an integer from 3 to 50, preferably from 4 to 45, more preferably from 5 to 40, even more preferably from 10 to 30. In a further embodiment, the present invention provides a stabilizing lipid selected from any one of SL1, SL2, SL3, SL4, SL5, SL6, SL7, SL8, SL9, SL10, SL11, SL12, SL13, SL14, SL15, SL16, -10- SL17, SL18, SL19, SL20, SL21, SL22, SL23, or SL24, wherein n and m are as defined in any one of the embodiments disclosed herein. In a further aspect, the present invention provides a method to prepare a lipid, in particular a 5 stabilizing lipid, as defined herein, said method comprising the steps of: a) providing first monomers comprising a zwitterionic moiety, in particular a phosphorylcholine moiety, represented by formula (VII) 10 wherein R3 is independently selected from -H, and -CH3; and X is selected from -O-, and -NH-; b) optionally providing one or more further monomers represented by formula (VIII) 15 wherein R3’ is independently selected from -H, and -CH3; and X’ is selected from -O-, and -NH-; c) providing an initiator, in particular a radical initiator; 20 d) providing a RAFT agent represented by formula (IX) -11- wherein R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1- 5 20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, - 10 OC(O)NR2-, -OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; each instance of R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2- 20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently 15 selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; 20 each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2- 20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, -O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and - 25 OC(O)-C2-20alkenyl; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and 30 Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and - C1-6alkyl; and e) performing reversible addition–fragmentation chain transfer (RAFT) polymerization by 35 heating a mixture of the first monomers, optionally the one or more further monomers, the initiator, and the RAFT agent, thereby providing the stabilizing lipid. -12- In a further aspect, the present invention provides a nanoparticle or nanoparticle composition comprising a lipid, in particular a stabilizing lipid as defined herein. Said nanoparticle composition may further comprise additional lipids either or not acting as stabilizers, such as an ionizable lipid, a helper lipid (e.g. a phospholipid) and / or a sterol. 5 In yet a further embodiment, the nanoparticle or nanoparticle composition as defined herein further comprises an active agent, in particular a nucleic acid, preferably mRNA. In a further aspect, the present invention provides the use of a lipid, in particular a stabilizing 10 lipid as defined herein in the manufacture of a nanoparticle or nanoparticle composition. In a final aspect, the present invention provides a pharmaceutical composition comprising one or more nanoparticles as defined herein and a pharmaceutically acceptable agent, such as a carrier, excipient, etc. Such pharmaceutical compositions are particularly suitable in various 15 fields such as prophylactic vaccines, therapeutic vaccines, protein replacement therapies, gene editing, gene silencing, small molecule delivery, etc. BRIEF DESCRIPTION OF THE DRAWINGS 20 Figure 1 (FIG.1) shows a representation of the physicochemical properties (size and PDI) of the LNPs according to Example 2a, measured via Zetasizer Nano (Malvern). Figure 2 (FIG.2) shows a representation of mRNA encapsulation efficiency of LNPs according to Example 2a, measured via Ribogreen. 25 Figure 3 (FIG.3) shows a representation of the zetapotential of LNPs according to Example 2a, measured via Zetasizer Nano (Malvern). Figure 4 (FIG.4) shows a representation of the impact of LNPs according to Example 2a on the 30 viability of the transfected HEK-293T cells. Figure 5 (FIG. 5) shows a representation of the Relative Mean Fluorescence Intensity (measured as the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2a at mRNA 35 concentration of 50 ng and 200 ng / well. Figure 6 (FIG.6) shows a representation of the physicochemical properties (size and PDI) of LNPs according to Example 2b, measured via Zetasizer Nano (Malvern). -13- Figure 7 (FIG.7) shows a representation of mRNA encapsulation efficiency of LNPs according to Example 2b, measured via Ribogreen. Figure 8 (FIG.8) shows a representation of zetapotential of LNPs according to Example 2b, 5 measured via Zetasizer Nano (Malvern). Figure 9 (FIG.9) shows a representation of the impact of LNPs according to Example 2b on the viability of the transfected HEK-293T cells. 10 Figure 10 (FIG. 10) shows a representation of the Relative Mean Fluorescence Intensity (measured as the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2b at mRNA concentration of 50 ng and 200 ng / well. 15 Figure 11 (FIG.11) shows a representation of the physicochemical properties (size and PDI) of the LNPs according to Example 2c, measured via Zetasizer Nano (Malvern). Figure 12 (FIG. 12) shows a representation of mRNA encapsulation efficiency of LNPs according to Example 2c, measured via Ribogreen. 20 Figure 13 (FIG.13) shows a representation of the zetapotential of LNPs according to Example 2c, measured via Zetasizer Nano (Malvern). Figure 14 (FIG.14) shows a representation of the cell viability of transfected HEK-293T cells 25 according to Example 2c. Figure 15 (FIG. 15) shows a representation of the Relative Mean Fluorescence Intensity (measured as the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2c at mRNA 30 concentration of 50 ng and 200 ng / well. Figure 16 (FIG.16) shows a representation of the physicochemical properties (size and PDI) of the LNPs according to Example 2d, measured via Zetasizer Nano (Malvern). 35 Figure 17 (FIG. 17) shows a representation of mRNA encapsulation efficiency of LNPs according to Example 2d, measured via Ribogreen. Figure 18 (FIG.18) shows a representation of the zetapotential of LNPs according to Example 2d, measured via Zetasizer Nano (Malvern). -14- Figure 19 (FIG.19) shows a representation of the cell viability of transfected HEK-293T cells according to Example 2d. 5 Figure 20 (FIG. 20) shows a representation of the Relative Mean Fluorescence Intensity (measured as the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2d at mRNA concentration of 50 ng and 200 ng / well. 10 Figure 21 (FIG.21) shows a representation of the in vivo average radiance as captured by the IVIS of the indicated LNPs according to Example 3a. Figure 22 (FIG. 22) shows a representation of the ex vivo average radiance of the liver, as captured by the IVIS of the indicated LNPs according to Example 3a. 15 Figure 23 (FIG.23) shows a representation of the in vivo average radiance as captured by the IVIS of the indicated LNPs according to Example 3b. Figure 24 (FIG.24) shows a representation of the average hEPO conc in the blood 6h after IV 20 injection of the indicated LNPs according to Example 3c. Figure 25 (FIG.25) shows a representation of the IgG1 titers at day 56 as determined by ELISA of the indicated LNPs according to Example 4a. 25 Figure 26 (FIG.26) shows a representation of the IgG2a titers at day 56 as determined by ELISA of the indicated LNPs according to Example 4a. Figure 27 (FIG. 27) shows a representation of the expression of IFNb as determined by LegendPlex 6 h post boost injection at day 56 of the indicated LNPs according to Example 4a. 30 Figure 28 (FIG. 28) shows a representation of the expression of IFNq as determined by LegendPlex 6 h post boost injection at day 56 of the indicated LNPs according to Example 4a. Figure 29 (FIG. 29) shows a representation of the expression of CXLC9 as determined by 35 LegendPlex 6 h post boost injection at day 56 of the indicated LNPs according to Example 4a. Figures 30 and 31 (FIG. 30 and FIG. 31) show a representation of the physicochemical properties (particle size and PDI) of the indicated LNP formulations at each timepoint after 4°C storage, as measured using a Zetasizer Nano (Malvern) according to Example 5. 40 -15- Figure 32 (FIG.32) shows a representation of mRNA encapsulation efficiency of LNPs at each timepoint after 4°C storage according to Example 5, measured via Ribogreen. 5 DETAILED DESCRIPTION OF THE INVENTION The present invention will now be further described. In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or 10 features indicated as being preferred or advantageous. When describing the compounds / lipids of the present invention, the terms used are to be construed in accordance with the following definitions, unless a context dictates otherwise: 15 The term "alkyl" by itself or as part of another substituent refers to a fully saturated hydrocarbon of Formula CxH2x+1 wherein x is a number greater than or equal to 1. Generally, alkyl groups of this invention comprise from 1 to 20 carbon atoms. Alkyl groups may be linear or branched and may be substituted as indicated herein. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. 20 Thus, for example, C1-4alkyl means an alkyl of one to four carbon atoms. Examples of alkyl groups are methyl, ethyl, n-propyl, i-propyl, butyl, and its isomers (e.g. n-butyl, i-butyl and t- butyl); pentyl and its isomers, hexyl and its isomers, heptyl and its isomers, octyl and its isomers, nonyl and its isomers; decyl and its isomers, undecyl and its isomers, dodecyl and its isomers, tridecyl and its isomers, tetradecyl and its isomers, pentadecyl and its isomers, hexadecyl and 25 its isomers, heptadecyl and its isomers, octadecyl and its isomers, nonadecyl and its isomers, eicosanyl and its isomers. The term "optionally substituted alkyl" refers to an alkyl group optionally substituted with one or more substituents (for example 1 to 4 substituents, for example 1, 2, 3, or 4 substituents) at any available point of attachment. 30 Whenever the term “substituted” is used in the present invention, it is meant to indicate that one or more hydrogens on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group, provided that the indicated atom’s normal valency is not exceeded, and that the substitution results in a chemically stable compound, i.e. a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, 35 and formulation into a therapeutic agent. Where groups may be optionally substituted, such groups may be substituted once or more, and preferably once, twice or thrice. Non-limiting examples of such substituents are selected from halogen (-halo), hydroxy (-OH), oxo (=O), nitro (-NO2), amino (-NR’R’’), cyano (-CN), alkyl, -16- cycloalkyl, alkenyl, alkynyl, alkoxy or aryloxy (-OR’’’), aryl, heteroaryl, carbonyl (-C(O)Riv), carboxyl (-COOH), ester or alkoxycarbonyl (-C(O)ORv), ester or alkylcarbonyloxy (-OC(O)Rvi), amido or aminocarbonyl (-NR’C(O)), amido or carbonylamino (-C(O)NR’), heterocyclyl, carbonyl, acyl, arylcarbonyl, thio (-SH), alkylthio (-SRvi), and the like. 5 The term "alkenyl" or “alkene”, as used herein, unless otherwise indicated, means straight-chain, cyclic, or branched-chain hydrocarbon radicals containing at least one carbon-carbon double bond. Examples of alkenyl radicals include ethenyl, E- and Z-propenyl, isopropenyl, E- and Z- butenyl, E- and Z-isobutenyl, E- and Z-pentenyl, E- and Z-hexenyl, E,E-, E,Z-, Z,E-, Z,Z- 10 hexadienyl, be it in the terminal or internal positions, and the like. Generally alkenyl or alkene moieties of the present invention comprise from 2 to 20 C atoms. An optionally substituted alkenyl refers to an alkenyl having optionally one or more substituents (for example 1, 2, 3 or 4), selected from those defined above for substituted alkyl. Unless stated otherwise, when a reference to "alkenyl" or “alkene”, it refers to all possible isomers of each of the carbon-carbon 15 double bonds present. The term "alkynyl", as used herein, unless otherwise indicated, means straight-chain or branched-chain hydrocarbon radicals containing at least one carbon-carbon triple bond. Examples of alkynyl radicals include ethynyl, propynyl, butynyl, pentynyl, hexynyl, hexadiynyl, 20 be it in the terminal or internal positions, and the like. An optionally substituted alkynyl refers to an alkynyl having optionally one or more substituents (for example 1, 2, 3 or 4), selected from those defined above for substituted alkyl. In the context of the present invention, the alkyl, alkenyl and alkynyl moieties as defined herein 25 may also further comprise one or more heteroatoms, such as selected from N, S or O, in that for example a carbon atom in an alkyl, alkene or alkyne chain is replaced by a heteroatom. When two or more C atoms are replaced by heteroatoms, the heteroatoms may be adjacent or separated, as long as it results in a chemically stable compound, i.e. a compound that is sufficiently robust to survive isolation to a useful degree of purity from a reaction mixture, and 30 formulation into a therapeutic agent. An example of a stable combination of two adjacent heteroatoms is a disulfide (-S-S-) group. Where a carbon atom in an alkyl, alkenyl or alkynyl chain is replaced by an N atom, the N atom may be N or NH depending on the number of bonds connected to said C atom. 35 The term “cycloalkyl” by itself or as part of another substituent is a cyclic alkyl group, that is to say, a monovalent, saturated, or unsaturated hydrocarbyl group having 1, 2, or 3 cyclic structure. Cycloalkyl includes all saturated or partially saturated (containing 1 or 2 double bonds) hydrocarbon groups containing 1 to 3 rings, including monocyclic, bicyclic, or polycyclic alkyl groups. Cycloalkyl groups may comprise 3 or more carbon atoms in the ring and generally, -17- according to this invention comprise from 3 to 15 atoms. Examples of cycloalkyl groups include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, adamantanyl and cyclodecyl. An “optionally substituted cycloalkyl” refers to a cycloalkyl having optionally one or more substituents (for example 1 to 3 substituents, for 5 example 1, 2, 3 or 4 substituents), selected from those defined above for substituted alkyl. Where alkyl groups as defined are divalent, i.e., with two single bonds for attachment to two other groups, they are termed "alkylene" groups. Non-limiting examples of alkylene groups includes methylene, ethylene, methylmethylene, trimethylene, propylene, tetramethylene, 10 ethylethylene, 1,2-dimethylethylene, pentamethylene and hexamethylene. Similarly, where alkenyl groups as defined above and alkynyl groups as defined above, respectively, are divalent radicals having single bonds for attachment to two other groups, they are termed "alkenylene" and "alkynylene" respectively. 15 The term “alkoxy" or “alkyloxy” as used herein refers to a radical having the Formula -OR’’’ wherein R’’’ is alkyl, alkenyl, or alkynyl. Non-limiting examples of suitable alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy. The term “aryloxy" as used herein refers to a radical having the Formula -OR’’’ wherein R’’’ is aryl. 20 Where the oxygen atom in an alkoxy group is substituted with sulfur, the resultant radical is referred to as alkylthio or arylthio, such as methylthio, ethylthio, phenylthio, and the like. The term “oxo” as used herein refers to the group =O. 25 The term "carbonyl" by itself or as part of another substituent refers to the group -C(O)Riv, wherein Rivis a hydrogen atom (i.e. an aldehyde), or alkyl, alkenyl, alkynyl or aryl (i.e. a ketone). The term "carboxy" or “carboxyl” or “hydroxycarbonyl” by itself or as part of another substituent 30 refers to the group -COOH, -C(O)OH, or -CO2H. The term "alkoxycarbonyl" by itself or as part of another substituent refers to a carboxy group linked to an alkyl radical i.e. to form -C(O)ORv, wherein Rvis alkyl, alkenyl, alkynyl or aryl. 35 The term “alkylcarbonyloxy” by itself or as part of another substituent refers to a -OC(O)Rviwherein Rviis alkyl, alkenyl, alkynyl or aryl. The term "heterocycle" as used herein by itself or as part of another group refers to non- aromatic, fully saturated or partially unsaturated cyclic groups (for example, 3 to 13 member -18- monocyclic, 7 to 17 member bicyclic, or 10 to 20 member tricyclic ring systems, or containing a total of 3 to 10 ring atoms) which have at least one heteroatom in at least one carbon atom- containing ring. Each ring of the heterocyclic group containing a heteroatom may have 1, 2, 3 or 4 heteroatoms selected from nitrogen atoms, oxygen atoms and / or sulfur atoms, where the 5 nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. The heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system, where valence allows. The rings of multi-ring heterocycles may be fused, bridged and / or joined through one or more spiro atoms. An optionally substituted heterocyclic refers to a heterocyclic having optionally one or more substituents (for example 1 10 to 4 substituents, or for example 1, 2, 3 or 4), selected from those defined above for substituted alkyl. Non-limiting examples of heterocycle comprise: piperidinyl, azepanyl, morpholinyl. The term “aryl" as used herein refers to a polyunsaturated, aromatic hydrocarbyl group having a single ring (i.e. phenyl) or multiple aromatic rings fused together (e.g. naphthalene or 15 anthracene) or linked covalently, typically containing 6 to 10 atoms; wherein at least one ring is aromatic. The aromatic ring may optionally include one to three additional rings (either cycloalkyl, heterocyclyl, or heteroaryl) fused thereto. Aryl is also intended to include the partially hydrogenated derivatives of the carbocyclic systems enumerated herein. Non-limiting examples of aryl comprise phenyl, napthyl, and the like. The aryl group or heterocycle as defined herein 20 can optionally be substituted by one or more substituents (for example 1 to 5 substituents, for example 1, 2, 3, 4 or 5) at any available point of attachment. Non-limiting examples of such substituents are selected from halogen, hydroxyl, oxo, nitro, amino, hydrazine, aminocarbonyl, azido, cyano, alkyl, cycloalkyl, alkenyl, alkynyl, cycloalkylalkyl, alkylamino, alkoxy, -SO2-NH2, aryl, heteroaryl, aralkyl, haloalkyl, haloalkoxy, alkoxycarbonyl, alkylaminocarbonyl, 25 heteroarylalkyl, alkylsulfonamide, heterocyclyl, alkylcarbonylaminoalkyl, aryloxy, alkylcarbonyl, acyl, arylcarbonyl, aminocarbonyl, alkylsulfoxide, -SO2Rx, alkylthio, carboxyl, and the like, wherein Rxis alkyl or cycloalkyl. The term “heteroaryl” as used herein by itself or as part of another group refers but is not limited 30 to 5 to 12 carbon-atom aromatic rings or ring systems containing 1 to 3 rings which are fused together or linked covalently, typically containing 5 to 8 atoms; at least one of which is aromatic in which one or more carbon atoms in one or more of these rings can be replaced by oxygen, nitrogen or sulfur atoms where the nitrogen and sulfur heteroatoms may optionally be oxidized and the nitrogen heteroatoms may optionally be quaternized. Such rings may be fused to an 35 aryl, cycloalkyl, heteroaryl or heterocyclyl ring. Non-limiting examples of such heteroaryl, include piridinyl, azepinyl. An “optionally substituted heteroaryl” refers to a heteroaryl having optionally one or more substituents (for example 1 to 4 substituents, for example 1, 2, 3 or 4), selected from those -19- defined above for substituted aryl. As used herein the terms such as “alkyl, aryl, or cycloalkyl, each being optionally substituted with” or “alkyl, aryl, or cycloalkyl, optionally substituted with” refers to optionally substituted alkyl, 5 optionally substituted aryl and optionally substituted cycloalkyl. The term “halo” or “halogen” as a group or part of a group is generic for fluoro, chloro, bromo, or iodo. 10 The term "direct bond" as used herein, refers to a chemical linkage directly connecting two or more specified moieties, without the presence of any intervening elements or groups. As used herein, when a compound has one or more stereocenters, each stereocenter may have the R or S configuration, unless stated otherwise. The compound may therefore be a racemic 15 mixture of enantiomers and / or diastereoisomers, or it may have an excess of one or more of the enantiomers and / or diastereoisomers, such as more than 60 %, more than 70 %, more than 80 %, more than 85 %, more than 90 %, more than 95 %, more than 98 %, more than 99 %. In the context of the present invention, the term lipid is meant to be a chemically defined 20 substance that is insoluble in water but soluble in amongst others alcohol, ether and chloroform. In the context of the present invention, the term ‘hydrophobic tail’ or ‘hydrophobic tail part’ is meant to be a chemically defined structure that is typically composed of hydrogen and carbon atoms, hence leading to a high degree of hydrophobicity, such as, but not limited to, alkyl, 25 alkenyl, and alkynyl groups. Each hydrophobic tail may be linear or branched. Each hydrophobic tail may further comprise one or more substantially hydrophobic functional groups, such as an ester moiety, an ether moiety, a sulfide moiety, a disulfide moiety, and the like. In the context of the present invention, the hydrophobic tail of the stabilizing lipids as defined herein is represented by the Q-R1 moiety 30 As already mentioned herein before, in a first aspect, the present invention provides a lipid, in particular a stabilizing lipid, represented by formula (I) -20- wherein n is an integer from 2 to 100; 5 m is 0, or an integer selected from 1 to 100; R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4;10 Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently 15 substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; 20 each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl 25 and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - -21- O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; 5 Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. 10 The lipid, in particular the stabilizing lipid, according to the present invention comprises: - a first oligomer or polymer part comprising structural units bearing a zwitterionic moiety, in particular a phosphorylcholine moiety; - optionally a second oligomer or polymer part comprising structural units not bearing a 15 zwitterionic moiety; and - a hydrophobic tail part. The structural units bearing a zwitterionic moiety, in particular a phosphorylcholine moiety, are the result of radical chain growth polymerization of the corresponding acrylate, methacrylate, 20 acrylamide or methacrylamide monomers. The structural units bearing a zwitterionic moiety, in particular a phosphorylcholine moiety, may be represented by formula (A) wherein 25 R3 is selected from -H, and -CH3; and X is selected from -O-, and -NH-. -22- The first oligomer or polymer part, as described herein, may contain any suitable number of structural units, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100 structural units. In useful embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, wherein n is an integer from 2 to 100, preferably from 3 to 50, 5 more preferably from 4 to 45, even more preferably from 5 to 40, yet even more preferably n is an integer from 10 to 30. In the context of the present invention, the terms “degree of polymerization” or “DP” refer to the number-averaged degree of polymerization. It generally refers to the number of monomeric units 10 in a polymeric molecule, or alternatively the average number of repeating units (monomers) in a polymer chain. It may be calculated using the equation: Mn / M0, where Mn is the number- averaged molecular weight of the polymer and M0 is the molecular weight of an individual structural unit. Alternatively, the degree of polymerization may be estimated by1H NMR. 15 The structural units not bearing a zwitterionic moiety, in particular a phosphorylcholine moiety, may be the result of radical chain growth polymerization of the corresponding acrylate or methacrylate monomers, or they may be the result of post-modification of the structural units bearing a zwitterionic moiety, in particular a phosphorylcholine moiety. The structural units not bearing a zwitterionic moiety may be represented by formula (B) 20 wherein R3’ is independently selected from -H, and -CH3; X’ is selected from -O-, and -NH-; and 25 SG represents a group resulting from the post-modification of the phosphorylcholine moiety, or a group which does not comprise a phosphorylcholine moiety. The second oligomer or polymer part, as described herein, is optional and may therefore be absent as a whole, i.e. wherein m is 0. The second oligomer or polymer part, as described 30 herein, may alternatively contain any suitable number of structural units, such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, or 100 structural units. In useful embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, wherein m is 0. In useful embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, wherein m is an integer from 1 to 100, preferably from 2 to 50, more 35 preferably from 3 to 45, even more preferably from 5 to 40, yet even more preferably m is an -23- integer from 10 to 30. The structural units not bearing a zwitterionic moiety may be the result of radical chain growth 5 polymerization of acrylate, methacrylate, acrylic acid, acrylamide and / or methacrylamide monomers known in the art, such as methyl methacrylate, ethyl acrylate, butyl acrylate, 2- ethylhexyl acrylate, acrylamide, methacrylamide, N-methyl acrylamide, N-ethyl acrylamide, and the like. 10 In embodiments of the present invention, SG is R6, wherein R6 is selected from -H, -C1-12alkyl, and -C2-12alkenyl. While in the formulae described herein, such as formula (I), the first oligomer or polymer part comprising structural units bearing a zwitterionic moiety, and the second oligomer or polymer 15 part comprising structural units not bearing a zwitterionic moiety, may be represented as blocks, the lipids of the invention are not limited thereto. In other words, when structural units not bearing a phosphorylcholine moiety are present (i.e. when m is not 0), structural units bearing a phosphorylcholine moiety, such as represented by formula (A), and structural units not bearing a phosphorylcholine moiety, such as represented by formula (B), may form a random co- 20 polymer, a gradient co-polymer or a block co-polymer. It was found that the lipid, in particular the stabilizing lipid, as defined herein, may be prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. RAFT is a reversible deactivation radical polymerization, also known as living or controlled radical polymerization, 25 achieved by degenerative transfer. Because here is no change in the overall number of radicals in a degenerative transfer system during the activation–deactivation process, a source of radicals such as a radical initiator is required. In RAFT polymerization a chain transfer agent (CTA), also known as RAFT agent, is used to control the equilibrium between active and dormant species. The RAFT agent typically comprises a thiocarbonylthio group, and may be represented 30 by the following formula: The Z-group is mostly responsible for the reactivity of the C=S bond toward radical addition and 35 governs the stability of the intermediate radical, which has to be considered relatively to the reactivity of the propagating radical. Acrylate and methacrylate monomers typically produce relatively more stabilized radicals and therefore require a Z-group that will help with the -24- stabilization of the intermediate radical to favor radical addition on the C=S. Therefore, trithiocarbonates (Z = S-alkyl) or dithiobenzoates (Z = Ph) RAFT agents are typically selected to control their polymerization. 5 The role of the R-group is typically much more subtle and affects the RAFT through (1) radical addition to the CTA; (2) subsequent fragmentation from the intermediate formed; and (3) propagation. Typically, good R-groups are groups that mimic monomer radicals or thermal initiators such as AIBN. 10 The R- and Z-C(S)S-groups of a RAFT agent, form the α and ω end-group of the majority of the polymeric chains resulting from the RAFT polymerization, respectively. The thiocarbonylthio group (Z-C(S)S-group) at the ω end of the oligomer or polymer part comprising structural units bearing a zwitterionic moiety, in particular a phosphorylcholine 15 moiety, and optionally structural units not bearing a zwitterionic moiety, of the lipid, in particular the stabilizing lipid, as defined herein, may have been removed or modified. It is known that a thiocarbonylthio end-group can, among others, be modified into a proton (-H), a hydroxy group (-OH), thiol (-SH), an iodo group (-I), an oxime, or an alkene. In the context of the present invention, Y1 may therefore be any thiocarbonylthio end-group resulting from the RAFT 20 polymerization, or any group obtained via (post-)modification of said thiocarbonylthio end-group, as mentioned hereinbefore. In embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, wherein 25 Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; and Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; As mentioned hereinbefore, the lipid, in particular the stabilizing lipid, according to the present invention comprises a hydrophobic tail part. This hydrophobic tail part is comprised in the R- 30 group at the α end of the oligomer or polymer part comprising structural units bearing a zwitterionic moiety, in particular a phosphorylcholine moiety, and optionally structural units not bearing a zwitterionic moiety, and may even be the whole R-group. In particular, the R-group at the α end of the oligomer or polymer part comprising structural units bearing a zwitterionic moiety, in particular a phosphorylcholine moiety, and optionally structural units not bearing a 35 zwitterionic moiety, comprising the lipid tail part, may be represented by formula (C) -25- wherein R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - 5 C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; 10 each instance of R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, - OC(O)-R5, and -C(O)O-R5; 15 the total number of C atoms in R1, and R2 together is at least 8; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl 20 and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; 25 Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 is a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl, in particular Ar1 is Ph. 30 In embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, represented by formula (I), and wherein one or more of the following applies: n is an integer from 2 to 100; 35 in particular n is an integer from 3 to 50; more in particular n is an integer from 4 to 45; -26- even more in particular n is an integer from 5 to 40; yet even more in particular n is an integer from 10 to 30; m is 0; or 5 m is an integer selected from 1 to 100; in particular m is an integer from 2 to 50; more in particular m is an integer from 3 to 45; even more in particular m is an integer from 5 to 40; yet even more in particular m is an integer from 10 to 30; 10 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; 15 in particular R1 is selected from -C1-20alkyl, and -C2-20alkenyl; wherein each of said -C1-20alkyl, and -C2-20alkenyl is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; more in particular R1 is selected from -C6-20alkyl, and -C6-20alkenyl; wherein each of said - C6-20alkyl, and -C6-20alkenyl is optionally and independently substituted with from 1 to 3 20 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; even more in particular R1 is selected from -C6-20alkyl, and -C6-20alkenyl; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; 25 in particular Q is selected from -C(O)NR2-, -OC(O)NR2-, and -C(O)O-; more in particular Q is selected from -C(O)NR2-, and -C(O)O-; each instance of R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently 30 comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, - OC(O)-R5, and -C(O)O-R5; in particular each instance of R2 is independently selected from -C1-20alkyl, and -C2-20alkenyl; wherein each of said -C1-20alkyl, and -C2-20alkenyl is optionally and independently substituted 35 with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; more in particular each instance of R2 is independently selected from -C6-20alkyl, and -C6- 20alkenyl; wherein each of said -C6-20alkyl, and -C6-20alkenyl is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; -27- even more in particular each instance of R2 is independently selected from -C6-20alkyl, and - C6-20alkenyl; the total number of C atoms in R1, and R2 together is at least 8; 5 in particular the total number of C atoms in R1, and R2 together is at least 10; more in particular the total number of C atoms in R1, and R2 together is at least 12; even more in particular the total number of C atoms in R1, and R2 together is from 14 to 46; yet even more in particular the total number of C atoms in R1, and R2 together is from 16 to 44; 10 yet even more in particular the total number of C atoms in R1, and R2 together is from 18 to 42; yet even more in particular the total number of C atoms in R1, and R2 together is from 20 to 40; 15 each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; 20 in particular each instance of R6 is independently selected from -C1-12alkyl; more in particular each instance of R6 is independently selected from -C1-8alkyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises 25 one or more heteroatoms selected from N, O and S; in particular L1is selected from a direct bond; -C1-12alkylene-, and -C2-12alkenylene; more in particular L1 is selected from a direct bond, -C1-6alkylene-, and -C2-6alkenylene; even more in particular L1 is selected from a direct bond, and -C1-3alkylene-; 30 each instance of R4and each instance R5is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, -O-C1-20alkyl, - O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; 35 in particular each instance of R4 and each instance R5 is independently selected from -C1- 20alkyl, and -C2-20alkenyl; wherein each of said -C1-20alkyl, and -C2-20alkenyl optionally and independently comprises one or more heteroatoms selected from O, N and S; more in particular each instance of R4and each instance R5is independently selected from -C1-20alkyl, and -C2-20alkenyl; -28- Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; in particular Y1 is selected from -SC(S)Ph, -H, -OH, and -SH; more in particular Y1 is selected from -H, -OH, and -SH; 5 Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; in particular Z is selected from -Ph, -Bn, and -S-C1-12alkyl; more in particular Z is selected from -Ph, and -S-C1-6alkyl; 10 Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; in particular Y2 is selected from -H, -CN, and -Ph; Y2’ is selected from -H, and -C1-6alkyl; 15 R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl; 20 in particular Ar1 and Ar2 are each independently Ph. In an embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (Ia) 25 wherein R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, Y1, Y2, Y2’, L1, Q, Z, Ar1, and Ar2 are as defined in any one -29- of the embodiments disclosed herein. In another embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (Ib) 5 wherein R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, Y1, Y2, Y2’, L1, Q, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. 10 In a further embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (II) 15 wherein -30- R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, X, X’, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. In a particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, 5 as defined herein and being represented by formula (IIa) wherein R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of 10 the embodiments disclosed herein. In another particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (IIb) 15 -31- wherein R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. 5 In a further embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (III) wherein 10 R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, X, X’, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. In a particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (IIIa) 15 -32- wherein R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. 5 In another particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (IIIb) wherein 10 R1, R2, R2’, R3, R3’, R4, R5, R6, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. In a further embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (IV) 15 -33- wherein R1, R2, R2’, R3, R4, R5, n, m, X, Y1, Y2, Y2’, L1, Q, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. 5 In a particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (IVa) wherein 10 R1, R2, R2’, R3, R4, R5, n, m, Y1, Y2, Y2’, L1, Q, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. In another particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (IVb) 15 -34- wherein R1, R2, R2’, R3, R4, R5, n, m, Y1, Y2, Y2’, L1, Q, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. 5 In a further embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (V) wherein 10 R1, R2, R2’, R3, R4, R5, n, m, X, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. In a particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (Va) 15 -35- wherein R1, R2, R2’, R3, R4, R5, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. 5 In another particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (Vb) 10 wherein R1, R2, R2’, R3, R4, R5, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. In a further embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as 15 defined herein and being represented by formula (VI)

[0003] -36- wherein R1, R2, R2’, R3, R4, R5, n, m, X, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the 5 embodiments disclosed herein. In a particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (VIa) 10 wherein R1, R2, R2’, R3, R4, R5, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments disclosed herein. 15 In another particular embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein and being represented by formula (VIb) -37- wherein R1, R2, R2’, R3, R4, R5, n, m, Y1, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the 5 embodiments disclosed herein. In specific embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, and being represented by any one of formula (I), (Ia), (Ib), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (IVa), (IVb), (V), (Va), (Vb), (VI), (VIa), or (VIb), wherein Y2 is -CN, and Y2’ is - 10 CH3. In specific embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, and being represented by any one of formula (I), (Ia), (Ib), (II), (IIa), (IIb), (III), (IIIa), (IIIb), (IV), (IVa), (IVb), (V), (Va), (Vb), (VI), (VIa), or (VIb), wherein Y2 is -H, and Y2’ is - 15 CH3. In a specific embodiment, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, and being selected from the list comprising:

[0004]

[0005] -44- wherein n and m are as defined in any one of the embodiments disclosed herein. In a more specific embodiment, the present invention provides a compound selected from any 5 of the tables disclosed herein. The stabilizing lipid of the present invention preferably has a number average molecular weight (Mn) of at most 30000 g / mol, preferably at most 25000 g / mol, more preferably at most 20000 g / mol, even more preferably at most 15000 g / mol, yet even more preferably of at most 10000 10 g / mol. The stabilizing lipid of the present invention preferably has a number average molecular weight (Mn) of at least 1000 g / mol, preferably at least 1500 g / mol, more preferably at least 2000 g / mol, even more preferably at least 2500 g / mol, yet even more preferably at least 3000 g / mol. In specific embodiments, the present invention provides a lipid, in particular a stabilizing lipid, as defined herein, wherein the number average molecular weight of the stabilizing lipid is from 1000 15 to 12000 g / mol, more preferably from 2000 to 10000 g / mol, even more preferably from 3000 to 9000 g / mol, yet even more preferably the number average molecular weight of the stabilizing lipid is from 4000 to 8000 g / mol. In a further aspect, the present invention provides a nanoparticle comprising a stabilizing lipid 20 as defined herein. In a particular embodiment a nanoparticle can comprise one or more of the stabilizing lipids of the invention in a liposomal structure, a bilayer, a micelle, a lamellar structure or any combination thereof. As used herein, the term "nanoparticle" refers to any particle having a diameter making the 25 particle suitable for systemic, in particular intravenous administration, of active agents typically having a diameter of less than 1000 nanometers (nm), preferably less than 500 nm, even more preferably less than 200 nm, such as for example between 50 and 200 nm; preferably between 80 and 160 nm. 30 In a very specific embodiment, the nanoparticle of the present invention may be in the form of a lipid nanoparticle or lipid nanoparticle composition comprising a lipid, in particular a stabilizing lipid as defined herein. In the context of the present invention, the term lipid nanoparticle (LNP), also termed solid lipid 35 nanoparticles (SLNP), is meant to be a nanoparticle comprising lipids. They are often used as a pharmaceutical drug delivery system or pharmaceutical formulation. LNPs as drug delivery vehicle were first approved in 2018 and are currently used in several candidate RNA based vaccines. A lipid nanoparticle is typically spherical with an average diameter between 10 and 1000 nanometers and possesses a lipid core matrix that can solubilize lipophilic molecules. The -45- term lipid is used here in a broader sense and includes triglycerides, diglycerides, monoglycerides, fatty acids, steroids (e.g. cholesterol) and waxes. Biological membrane lipids such as phospholipids, sphingomyelins, bile acids and sterols are typically used as stabilizers in LNPs. In a particular embodiment, the term lipid nanoparticle (LNP) excludes liposomes. 5 In a further aspect, the present invention provides a nanoparticle or nanoparticle composition comprising a lipid, in particular a stabilizing lipid, as defined herein. Said nanoparticle composition may further comprise additional lipids either or not acting as stabilizers, such as an ionizable lipid, a helper lipid (e.g. a phospholipid) and / or a sterol. 10 Accordingly, in the context of the present invention, the nanoparticles as disclosed herein further comprise additional lipids either or not acting as stabilizers, such as an ionizable lipid, a helper lipid (e.g. a phospholipid) and / or a sterol. 15 Alternatively, the nanoparticles of the present invention may be in any other suitable form such as in the form of a liposome, a lipid nanoemulsion (LNE), a nanostructured lipid carrier (NLC), a hybrid lipid-polymeric nanoparticle, or a hybrid lipid-metal nanoparticle. In the context of the invention, a liposome is a nanoparticle in the form of a lipid bilayer structure. 20 Such liposomes are typically composed of phospholipids and cholesterol, and are in the present invention combined with one or more stabilizing lipids as defined herein. LNEs consist of submicron sized lipid droplets, stabilized by surfactants in an aqueous solution. LNEs for medical use mostly consist of plant-based lipid droplets stabilized by other lipids such as phospholipids and / or ionizable lipids. NLCs are regarded as an alternative SLNP in which solid lipid 25 components are replaced by liquid lipids, thereby resulting in a larger loading capacity for active agents. Hybrid LNPs typically consist of a therapeutic-containing polymeric core enveloped by an inner lipid layer and an outer lipid layer, the latter one often containing PEGylated lipids. Due to the characteristics of both lipids and polymers, these hybrid LNPs present great stability, sustained release and high biocompatibility. Hybrid lipid-metal nanoparticles may be obtained 30 by coating metal nanoparticles with lipids, thereby resulting in improved biocompatibility, nanoparticle stability and endocytosis efficiency. Suitable hybrid lipid-metal nanoparticles are for example hybrid lipid-coated silver nanoparticles (lipid-AgNPs), lipid-aluminum nanoparticles, and liposome gold nanoparticles (LiposAu NPs). 35 In the context of the present invention, the term “ionizable lipid” or alternatively “cationic lipid” means the presence of any uncharged group in said lipid which is capable of dissociating by yielding an ion (usually an H+ion) and thus itself becoming positively charged. Alternatively, any uncharged group in said compound or lipid may yield an electron and thus becoming negatively charged. -46- In the context of the present invention, the term “PEG lipid” or alternatively “PEGylated lipid” is meant to be any suitable lipid modified with a polyethylene glycol (PEG) group. 5 In the context of the present invention, the term “phospholipid” is meant to be a lipid molecule consisting of two hydrophobic fatty acid “tails” and a hydrophilic “head” consisting of a phosphate group. The two components are most often joined together by a glycerol molecule, hence, the phospholipid of the present invention is preferably a glycerol-phospholipid. Furthermore, the phosphate group is often modified with simple organic molecules such as choline (i.e. rendering 10 a phosphocholine) or ethanolamine (i.e. rendering a phosphoethanolamine). In the context of the present invention, the term “sterol”, also known as steroid alcohol, is a subgroup of steroids that occur naturally in plants, animal and fungi, or can be produced by some bacteria. In the context of the present invention, any suitable sterol may be used, such as 15 selected from the list comprising cholesterol, ergosterol, campesterol, oxysterol, antrosterol, desmosterol, nicasterol, sitosterol and stigmasterol; preferably cholesterol. In yet a further embodiment of the present invention, the nanoparticle nanoparticle composition as defined herein further comprises a cargo molecule such as a pharmaceutically active agent 20 (e.g. small molecule) or a biomolecule, such as a peptide, protein or a nucleic acid. Accordingly, the nanoparticles and nanoparticle compositions of the present invention are particularly suitable for the intracellular delivery of their cargo molecules. Hence, the present invention provides the use of the nanoparticles and nanoparticle compositions as defined herein for the intracellular delivery of cargo molecules. 25 In a particular embodiment, the nanoparticle or nanoparticle composition as defined herein further comprises an active agent, such as a small molecule, a therapeutic peptide, a therapeutic protein, a nucleic acid, or any combination thereof. 30 In a particular embodiment, the active agent of the present invention is a therapeutic nucleic acid. A “nucleic acid” in the context of the invention may include deoxyribonucleic acid, ribonucleic acid, recombinantly produced and chemically synthesized molecules. In particular a nucleic acid 35 may include DNA, genomic DNA, cDNA, RNA, mRNA, small interfering RNA (siRNA), micro RNA (miRNA), antisense oligonucleotides, ribozymes, plasmids, immune stimulating nucleic acids, antisense nucleic acids, antagomirs (anti-miRs), miRs, supermiRs, U1 adaptors, and aptamers. -47- A nucleic acid may according to the invention be in the form of a molecule which is single stranded or double stranded and linear or closed covalently to form a circle. A nucleic acid can be employed for introduction into, i.e. transfection of cells, for example, in the form of RNA which can be prepared by in vitro transcription from a DNA template. The RNA can moreover be 5 modified before application by stabilizing sequences, capping, and / or polyadenylation. In the context of the present invention, the term "RNA" relates to a molecule which comprises ribonucleotide residues and preferably being entirely or substantially composed of ribonucleotide residues. "Ribonucleotide" relates to a nucleotide with a hydroxyl group at the 2'-position of a β- 10 D-ribofuranosyl group. The term includes double stranded RNA, single stranded RNA, isolated RNA such as partially purified RNA, essentially pure RNA, synthetic RNA, recombinantly produced RNA, as well as modified RNA that differs from naturally occurring RNA by the addition, deletion, substitution and / or alteration of one or more nucleotides. Such alterations can include addition of non-nucleotide material, such as to the end(s) of a RNA or internally, for 15 example at one or more nucleotides of the RNA. Nucleotides in RNA molecules can also comprise non-standard nucleotides, such as non-naturally occurring nucleotides or chemically synthesized nucleotides or deoxynucleotides. These altered RNAs can be referred to as analogs. Nucleic acids may be comprised in a vector. The term "vector" as used herein includes any vectors known to the skilled person including plasmid vectors, cosmid vectors, phage 20 vectors such as lambda phage, viral vectors such as adenoviral or baculoviral vectors, or artificial chromosome vectors such as bacterial artificial chromosomes (BAC), yeast artificial or analogs of naturally-occurring RNA. According to the present invention, the term "RNA" includes and preferably relates to "mRNA" which means "messenger RNA" and relates to a "transcript" which may be produced using DNA 25 as template and encodes a peptide or protein. mRNA typically comprises a 5' untranslated region (5’ -UTR), a protein or peptide coding region and a 3' untranslated region (3'-UTR). mRNA has a limited halftime in cells and in vitro. Preferably, mRNA is produced by in vitro transcription using a DNA template. In one embodiment of the invention, the RNA is obtained by in vitro transcription or chemical synthesis. The in vitro transcription methodology is known to the skilled 30 person. For example, there is a variety of in vitro transcription kits commercially available. In a further aspect, the present invention provides a pharmaceutical composition comprising one or more nanoparticles as defined herein and a pharmaceutically acceptable agent, such as a carrier, excipient, etc. 35 The present invention also provides the nanoparticles and pharmaceutical compositions according to this invention for use in human or veterinary medicine. The use of nanoparticles and pharmaceutical compositions according to this invention for human or veterinary medicine -48- is also intended. In addition, the invention provides a method for the prophylaxis and treatment of human and veterinary disorders, by administering the nanoparticles or pharmaceutical compositions according to this invention to a subject in need thereof. 5 Such pharmaceutical compositions are particularly suitable in various fields such as prophylactic vaccines, therapeutic vaccines, protein replacement therapies, gene editing, gene silencing, small molecule delivery, etc. In a specific aspect, the nanoparticles and pharmaceutical compositions as defined herein may 10 be used in the induction of an immune response in a subject by providing to the subject a pharmaceutical composition wherein the active agent is an immunostimulatory oligonucleotide. For example, the invention provides a vaccine comprising one or more nanoparticles according to the present invention. To that end, a vaccine as meant herein contains at least one active agent, such as a nucleic acid molecule, e.g. mRNA molecule encoding an antigen to which an 15 adaptive immune response is mounted. This antigen can be present in the format of a weakened or killed form of a microbe, a protein or peptide, or an antigen encoding a nucleic acid, such as a disease-associated antigen for example a tumor antigen. Vaccines can be prophylactic (example: to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (example, to actively treat or reduce the symptoms of an ongoing 20 disease). In another aspect, the nanoparticles and pharmaceutical compositions as defined herein may be used in the treatment of a disease or disorder characterized by the overexpression of a polypeptide in a subject by providing to the subject a pharmaceutical composition of the present invention, wherein the active agent is a nucleic acid selected from an siRNA, a microRNA, and 25 an antisense oligonucleotide, and wherein the siRNA, microRNA, or antisense oligonucleotide includes a polynucleotide that specifically binds to a polynucleotide that encodes the polypeptide, or a complement thereof. In a preferred embodiment, the nucleic acid is a siRNA or miRNA. In another aspect, the nanoparticles and pharmaceutical compositions as defined herein may 30 be used in the treatment of a disease or disorder characterized by underexpression of a polypeptide in a subject by providing to the subject a pharmaceutical composition of the present invention, wherein the active agent is a plasmid that encodes the polypeptide or a functional variant or fragment thereof, such as in the context of protein replacement therapy. In yet a further aspect, the nanoparticles and compositions as defined herein may be used as a 35 transfection agent that includes the compositions or nanoparticles described herein, wherein the composition or nanoparticles include a nucleic acid. The agent, when contacted with cells, can -49- efficiently deliver nucleic acids to the cells. Yet another aspect is a method of delivering a nucleic acid to the interior of a cell, by obtaining or forming a composition or nanoparticles described herein and contacting the composition or lipid particles with a cell. In a very specific embodiment, the present invention provides the nanoparticles and 5 pharmaceutical compositions of the present invention for use in the treatment of cancer or infectious diseases. In yet a further aspect, the present invention provides a method to prepare the lipids, in particular the stabilizing lipids, as defined herein, said method comprising the steps of: 10 a) providing first monomers comprising a zwitterionic moiety, in particular a phosphorylcholine moiety, represented by formula (VII) wherein 15 R3 is independently selected from -H, and -CH3; and X is selected from -O-, and -NH-; b) optionally providing one or more further monomers represented by formula (VIII) 20 wherein R3’ is independently selected from -H, and -CH3; and X’ is selected from -O-, and -NH-; c) providing an initiator, in particular a radical initiator; -50- d) providing a RAFT agent represented by formula (IX) wherein 5 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1- 20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; 10 Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, - OC(O)NR2-, -OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; each instance of R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2- 20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is 15 optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally 20 further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2- 20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 325 substituents selected from -OH, -O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and - OC(O)-C2-20alkenyl; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; 30 R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and - C1-6alkyl; and -51- e) performing reversible addition–fragmentation chain transfer (RAFT) polymerization by heating a mixture of the first monomers, optionally the one or more further monomers, the initiator, and the RAFT agent, thereby providing the stabilizing lipid. Any initiator, in particular any radical initiator, suitable for RAFT polymerization may be used in 5 the method as defined herein. It was found that 4,4'-azobis(4-cyanovaleric acid) is particularly suited for the method as defined herein. In specific embodiments, the present invention provides the method as defined herein, wherein one or more of the following applies: 10 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; 15 in particular R1 is selected from -C1-20alkyl, and -C2-20alkenyl; wherein each of said -C1-20alkyl, and -C2-20alkenyl is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; more in particular R1 is selected from -C6-20alkyl, and -C6-20alkenyl; wherein each of said - C6-20alkyl, and -C6-20alkenyl is optionally and independently substituted with from 1 to 3 20 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; even more in particular R1 is selected from -C6-20alkyl, and -C6-20alkenyl; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; 25 in particular Q is selected from -C(O)NR2-, -OC(O)NR2-, and -C(O)O-; each instance of R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and30 independently substituted with from 1 to 3 substituents independently selected from -OH, - OC(O)-R5, and -C(O)O-R5; in particular each instance of R2 is independently selected from -C1-20alkyl, and -C2-20alkenyl; wherein each of said -C1-20alkyl, and -C2-20alkenyl is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5;35 more in particular each instance of R2 is independently selected from -C6-20alkyl, and -C6- 20alkenyl; wherein each of said -C6-20alkyl, and -C6-20alkenyl is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; -52- even more in particular each instance of R2 is independently selected from -C6-20alkyl, and - C6-20alkenyl; the total number of C atoms in R1, and R2 together is at least 8; 5 in particular the total number of C atoms in R1, and R2 together is at least 10; more in particular the total number of C atoms in R1, and R2 together is at least 12; even more in particular the total number of C atoms in R1, and R2 together is from 14 to 46; yet even more in particular the total number of C atoms in R1, and R2 together is from 16 to 44; 10 yet even more in particular the total number of C atoms in R1, and R2 together is from 18 to 42; yet even more in particular the total number of C atoms in R1, and R2 together is from 20 to 40; 15 each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; 20 in particular each instance of R6 is independently selected from -C1-12alkyl; more in particular each instance of R6 is independently selected from -C1-8alkyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises 25 one or more heteroatoms selected from N, O and S; in particular L1is selected from a direct bond; -C1-12alkylene-, and -C2-12alkenylene; more in particular L1 is selected from a direct bond, -C1-6alkylene-, and -C2-6alkenylene; even more in particular L1 is selected from a direct bond, and -C1-3alkylene-; 30 each instance of R4and each instance R5is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, -O-C1-20alkyl, - O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; 35 in particular each instance of R4 and each instance R5 is independently selected from -C1- 20alkyl, and -C2-20alkenyl; wherein each of said -C1-20alkyl, and -C2-20alkenyl optionally and independently comprises one or more heteroatoms selected from O, N and S; more in particular each instance of R4and each instance R5is independently selected from -C1-20alkyl, and -C2-20alkenyl; -53- Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; in particular Y1 is selected from -SC(S)Ph, -H, -OH, and -SH; more in particular Y1 is selected from -H, -OH, and -SH; 5 Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; in particular Z is selected from -Ph, -Bn, and -S-C1-12alkyl; more in particular Z is selected from -Ph, and -S-C1-6alkyl; 10 Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; in particular Y2 is selected from -H, -CN, and -Ph; Y2’ is selected from -H, and -C1-6alkyl; 15 R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl; 20 in particular Ar1 and Ar2 are each independently Ph. In an embodiment, the present invention provides the method as defined herein, wherein the first monomers provided in step a) are represented by formula (VIIa) or (VIIb) 25 wherein R3 is as defined in any one of the embodiments disclosed herein. -54- In a further embodiment, the present invention provides the method as defined herein, wherein the one or more further monomers provided in step b) are represented by formula (VIIIa) or (VIIIb) (VIIIa) (VIIIb) 5 wherein R3’, and R6 are as defined in any one of the embodiments disclosed herein. In a further embodiment, the present invention provides the method as defined herein, wherein 10 the RAFT agent provided in step d) is represented by formula (X) or (XI) wherein R1, R2, R2’, R4, R5, Y2, Y2’, L1, Z, Ar1, and Ar2 are as defined in any one of the embodiments 15 disclosed herein. In specific embodiments, the present invention provides the method as defined herein, wherein the RAFT agent provided in step d) is represented by any one of formula (IX), (X) or (XI), wherein Y2 is -CN, and Y2’ is -CH3. 20 In specific embodiments, the present invention provides the method as defined herein, wherein the RAFT agent provided in step d) is represented by any one of formula (IX), (X) or (XI), wherein Y2 is -H, and Y2’ is -CH3. 25 In an embodiment, the present invention provides the method as defined herein, comprising a further step of modifying the thiocarbonylthio group of the stabilizing lipid. In an embodiment, the present invention provides the method as defined herein, comprising a further step of modifying one or more of the phosphorylcholine moieties of the stabilizing lipid. 30 The stabilizing lipids of the present invention can be prepared according to the reaction schemes provided in the examples hereinafter, but those skilled in the art will appreciate that these are -55- only illustrative for the invention. EXAMPLES 5 EXAMPLE 1: PREPARATION OF THE LIPIDS 1. General information Unless otherwise stated, all glassware was oven dried before use and all reactions were carried out under an argon atmosphere using standard Schlenk-techniques. Dry solvents were purchased from Acros Organics or Sigma-Aldrich and used without further purification. All 10 reagents were purchased from commercial sources and were used without further purification unless otherwise stated. Amines were purchased from commercial sources, or prepared according to methods described in WO2022136641. Reaction progress was monitored by thin layer chromatography (TLC) performed on aluminum plates coated with Kieselgel F254 with 0.2 mm thickness. Visualization was achieved by ultraviolet light (254 nm) or by staining with 15 potassium permanganate. Flash column chromatography was performed using silica gel 60 (230-400 mesh, Merck ans co.). Mass spectra were obtained using a Finnigan MAT 8200 (70 eV), an Agilent 5973 (70 eV), using electrospray ionization (ESI) or electron impact ionization (EI). All1H NMR,13C NMR were recorded on a BrukerAV-400 in Chloroform-d1 or DMSO-d6. Chemical shifts are given in parts per million (ppm), referenced to tetramethylsilane using the 20 solvent peak as internal standard (CDCl3:1H = 7.26 ppm,13C = 77.16 ppm; CD3SOCD3:1H = 2.50 ppm,13C = 39.52 ppm). Coupling constants were quoted in Hz.1H NMR splitting patterns were designated as singlet (s), broad (brd), doublet (d), triplet (t), quartet (q), pentet (p), sextet (se), septet (sep), octet (o) or combinations thereof. Splitting patterns that could not be interpreted were designated as multiplet (m). 25 2. Synthesis of lipids 2.1 Synthesis of hydrophobic tail fragments 2.1.1 General route A1 for the synthesis of hydrophobic tail fragment 1 is shown below (Alk is alkyl, alkenyl, or alkynyl). -56- 2.1.2 General route A2 for the synthesis of hydrophobic tail fragment 2 is shown below (Alk is alkyl, alkenyl, or alkynyl). -57- 2.2 Synthesis of CTA-lipids 2.2.1 General route B1 for the synthesis of CTA-lipid 1 is shown below (Alk is alkyl, alkenyl, or alkynyl) 5

[0006] -58- 2.2.2 General route B2 for the synthesis of CTA-lipid 1 is shown below (Alk is alkyl, alkenyl, or alkynyl)1,2 5 2.2.3 General route B3 for the synthesis of CTA-lipid 2 is shown below (Alk is alkyl, alkenyl, or alkynyl) 2.3 Synthesis of stabilizing lipids 10 2.3.1 General route C1 for the synthesis of stabilizing lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl) -59- 2.3.2 General route C2 for the synthesis of stabilizing lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl) 5 2.4 Post-modification of thiocarbonylthio group 2.4.1 General route D1 for the synthesis of stabilizing lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl)310

[0007] -60- 2.4.2 General route D2 for the synthesis of stabilizing lipids according to formula (I) is shown below (Alk is alkyl, alkenyl, or alkynyl) 5 Example 1a A CTA-lipid was prepared according to general route B1 and was subsequently used to prepare stabilizing lipids according to general route C1, wherein the stabilizing lipids have a different degree of polymerization. 10

[0008] -61- 5 Under inert atmosphere (Ar), 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CTA, 1 eq., 0.717 mmol) and N-hydroxysuccinimide (NHS, 1.2 eq., 0.860 mmol) were dissolved in dry DCM (5 mL). Separately, under Ar, N,N'-dicyclohexylcarbodiimide (DCC, 1.2 eq., 0.860 mmol) was dissolved in dry DCM (5 mL). The latter was transferred dropwise into the CTA solution under stirring using an Ar purged syringe. The reaction was stirred for 12 hours at room temperature 10 in a flask covered with Al foil to avoid light exposure. Then, a solution of lipid-amine (1.5 eq., 1.08 mmol) in dry DCM (3 mL) was transferred into the mixture while stirring. The reaction proceeded for 24h in the Al foil covered flask. The crude mixture was purified through silica gel flash chromatography. The solvent was removed under reduced pressure yielding a red oil. The product was analysed through mass spectroscopy (m / z: 671.1) and 1H NMR (300 MHz, 15 chloroform-d): δ 7.89 (d, J = 7.3 Hz, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.44 – 7.32 (m, 2H), 3.25 (s, 4H), 2.63 (s, 4H), 1.94 (s, 3H), 1.25 (s, 52H), 0.86 (s, 6H). -62- Stabilizing lipids In a Schlenk tube, 2-methacryloyloxyethyl phosphorylcholine (MoPC, previously purified to remove inhibitor by washing with Et2O and dried under high vacuum) and CTA-lipid 1a were 5 solubilized in EtOH. The mixture was stirred at 0°C until complete dissolution of the reactants. 4,4'-Azobis(4-cyanovaleric acid) (V-501) dissolved in DMF was added to the mixture, at 0°C, while stirring. Ar gas was bubbled into the mixture at 0 °C for 30 minutes. Then, the solution was transferred into a pre-heated oil bath at 70°C. The reaction proceeded until desired conversion, checked through1H NMR. Purification occurred via dialysis against ethanol, then mQ water, 10 using an appropriate membrane cut-off based on the polymer molecular weight. The obtained polymer was then freeze dried. Table 1 provides an overview of the amount of reagents used to prepare stabilizing lipids according to example 1a with a different degree of polymerization. 15 Table 1. Overview of reagents to prepare the stabilizing lipids according to Example 1a The degree of polymerization of the different stabilizing lipids, shown as the number of structural units (n) resulting from the polymerization of MoPC monomers, was estimated by1H NMR 20 analysis. The estimated DP of the different stabilizing lipids is shown in Table 2. -63- Table 2. Overview of estimated degree of polymerization of the stabilizing lipids according to Example 1a Example 1b 5 Specific stabilizing lipids prepared according to Example 1a were post-modified according to ZP2 was solubilized in mQ water (reaching a 12.5 mg / mL) and H2O2 was added to the mixture 10 in a ratio 10:1 H2O2:CTA moiety. The mixture was then placed in a pre-heated oil bath at 70°C, in open air, and stirred for 3 h. The polymer was then purified through dialysis and1H NMR analysis was performed to evaluate the removal of the dithiobenzoate group by checking the aromatic region at 7-8 ppm. Purification occurred via dialysis against ethanol, then mQ water, using an appropriate membrane cut-off based on the polymer molecular weight. The obtained 15 polymer, ZP3, was then freeze dried. In a similar way, ZP4 was converted into ZP5. The degree of polymerization of ZP3 and ZP5 is the same as ZP2 and ZP4, respectively, and shown in Table 3. Table 3. Overview of estimated degree of polymerization of the stabilizing lipids according to 20 Example 1b -64- Example 2a A CTA-lipid was prepared according to general route B3 and was subsequently used to prepare stabilizing lipids according to general route C1, wherein the stabilizing lipids have a different 5 degree of polymerization. 10 -65- CTA- lipid 2a In Ar condition, 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CTA) (500 mg, 1 eq., 1.79 mmol), DMAP (21.9 mg, 0.1 eq., 0.179 mmol) and Octadecan-1-ol (483 mg, 1.79 mmol, 1 eq.) 5 were dissolved in dry DCM (7.0 mL) and let stirred for 5 minutes, in the dark. To the stirring solution, N,N' dicyclohexylcarbodiimide DCC (406 mg, 1.1 eq., 1.97 mmol), solubilized in dry DCM (3.0) mL, was slowly added at room temperature to the CTA-containing solution. The mixture was then let to stir overnight at room temperature. After this time, the mixture was filtered to remove urea byproduct, and the solvent removed under reduced pressure to obtain a red oil. 10 The recovered crude mixture was then purified through silica gel flash chromatography two times (eluents hexane:EtOAc 7:3, then DCM Hexane 7:3). The solvent was removed under reduced pressure yielding a red oil as purified product (60% yield). The product was then analysed through mass spectroscopy ([M+H+]: 532.4 m / z, [M+K+]: 570.3 m / z) and 1H NMR (400 MHz, Chloroform-d) δ 7.91 (dd, J = 8.5, 1.4 Hz, 2H), 7.63 – 7.54 (m, 1H), 7.46 – 7.36 (m, 2H), 4.10 (t, 15 J = 6.8 Hz, 2H), 2.79 – 2.37 (m, 4H), 1.94 (s, 3H), 1.63 (t, J = 7.2 Hz, 2H), 1.26 (s, 30H), 0.88 (t, J = 6.7 Hz, 3H). Stabilizing lipids 20 In a Schlenk tube, 2-methacryloyloxyethyl phosphorylcholine (MoPC, previously purified to remove inhibitor by washing with Et2O and dried under high vacuum) (666.9 mg, 40 eq) and CTA-lipid 1b (30.0 mg, 1 eq.) were solubilized in EtOH (1.7 mL). The mixture was stirred at 0°C until complete dissolution of the reactants.4,4'-Azobis(4-cyanovaleric acid) (V-501, 1.58 mg, 0.1 eq.) dissolved in DMF (212 µL) was added to the mixture, at 0°C, while stirring. Ar gas was25 bubbled into the mixture at 0 °C for 30 minutes. Then, the solution was transferred into a pre- heated oil bath at 70°C. The reaction proceeded until desired conversion, checked through1H -66- NMR. Purification occurred via dialysis against ethanol, then mQ water, using an appropriate membrane cut-off based on the polymer molecular weight. The obtained polymer was then freeze dried. 5 The estimated DP of the different stabilizing lipids is shown in Table 4. Table 4. Overview of estimated degree of polymerization of the stabilizing lipids according to Example 2a 10 Example 2b Specific stabilizing lipids prepared according to Example 2a were post-modified according to general route D1. 15 ZP7 was solubilized in mQ water (reaching a 12.5 mg / mL) and H2O2was added to the mixture in a ratio 10:1 H2O2:CTA moiety. The mixture was then placed in a pre-heated oil bath at 70°C, in open air, and stirred for 3 h. The polymer was then purified through dialysis and1H NMR analysis was performed to evaluate the removal of the dithiobenzoate group by checking the aromatic region at 7-8 ppm. Purification occurred via dialysis against ethanol, then mQ water, 20 using an appropriate membrane cut-off based on the polymer molecular weight. The obtained -67- polymer, ZP8, was then freeze dried. In a similar way, ZP10 was converted into ZP11, and ZP13 into ZP14. The degree of polymerization of ZP8, ZP11 and ZP14 is the same as ZP7, ZP10 and ZP13, respectively, and shown in Table 5. 5 Table 5. Overview of estimated degree of polymerization of the stabilizing lipids according to Example 2b 10 EXAMPLE 2: IN VITRO EXPERIMENTS Materials and methods mRNA synthesis mRNA encoding for eGFP was prepared in vitro by T7-mediated transcription from linearized DNA templates (peTheRNAvs3 vector), which incorporates 5’ and 3’ UTRs and a polyA tail. The 15 final mRNA utilizes Cap1 and 100% replacement of uridine with N1-methyl-pseudo-uridine. LNP synthesis Lipid based nanoparticles are produced by microfluidic or T-junction mixing of an mRNA solution in a citrate (25 mM, pH 3) or sodium acetate buffer (100mM, pH4) and lipid solution in a 3:1 volume ratio at a speed of 9 mL / min, 12 mL / min,16 ml / min or 20 mL / min using the NanoAssemblr 20 Benchtop (Precision Nanosystems) or alternative T-junction device. The lipid solution contained a mixture of the ionizable lipid of interest, DSPC or DOPE (Avanti), Cholesterol (Sigma) and DMG-PEG2000 (Avanti) or stabilizing lipids prepared according to the examples disclosed herein. LNPs were dialyzed against TBS (10000 times more TBS volume than LNP volume) using slide-a-lyzer dialysis cassettes (20K MWCO, 3mL, ThermoFisher). Size, polydispersity 25 and zeta potential were measured with a Zetasizer Nano (Malvern). mRNA encapsulation was measured by standard Ribogreen RNA assay (Invitrogen). The apparent pKa of formulated LNPs was determined via TNS binding assay as described by Sabnis et al. (Molecular Therapy, Vol.26, No 6, 2018). 30 -68- Cell lines The most optimal culturing conditions per cell type including growth medium, sub cultivation ratio, and medium renewal recommendations are summarized below. To harvest adherent cells, used-up growth medium was discarded and cells were rinsed twice with phosphate buffered 5 saline (PBS) (Sigma) before addition of trypsine-EDTA (0.05%) (Gibco, Thermo Fisher Scientific) to loosen the cells. Medium renewal needs to occur every 2 to 3 days, whenever cells reached confluency of approximately 70%. Cell viability was determined using the Vi-Cell XR Cell Viability Analyzer (Beckman Coulter). 10 Abbreviations: DMEM: Dulbecco’s Modified Eagle Medium; P / S: Penicillin / Streptomycin; FBS: Fetal Bovine Serum Transfection Cells were plated in a 96-well plate at a density of 2.0-3.0 x10e4 cells / 100µl complete growth 15 medium (specific per cell type). Transfection was performed when cells reached 70-90% confluency. The positive control Lipofectamine (MessengerMAX, Invitrogen) was diluted in OptiMEM (serum reduced, Gibco) and incubated for 10 minutes. In the meantime, eGFP mRNA and LNPs encapsulating eGFP mRNA were diluted in OptiMEM to get to a concentration of the mRNA content of 200 and 50 ng / well. mRNA : lipid complexes were incubated in a 1 : 1 ratio for 20 5 minutes and were added to each condition in quadruplicate. Cells were incubated for 24 hours at 37°C 5% CO2. Afterwards cells were harvested using 1 x TrypLE select enzyme (Gibco) and stained with a live / dead marker SYTOX blue (Life Technologies) in FACS buffer (PBS supplemented with 1% bovin serum albumin (BSA) and 0.09% azide (all from Sigma)). Cells were immediately acquired after addition of the live dead marker using the Attune Nxt Flow 25 Cytometer (ThermoFisher Scientific). eGFP expression For assessment of eGFP expression, cells were stained with SYTOX blue. Within the gate of SYTOX blue negative cells, expression levels of eGFP were determined. The relative mean 30 fluorescence intensity (rel MFI) was calculated as the MFI value of the expression marker divided by that of untransfected cells. -69- Data was acquired on an Attune Nxt cytometer and analyzed with Flow Jo Software. Flow cytometric data were analyzed using the Flowjo version 10 software. Example 2a 5 LNPs were produced at a standard molar ratio ionizable lipid / DSPC / cholesterol / DMG-PEG2000 or PEG-alternative of about 50 / 10 / 38.5 / 1.5. MC3 was used as ionizable lipid. eGFP mRNA was encapsulated in all LNPs as reporter mRNA, at a mRNA / ionizable lipid molar ratio of 1 / 6. A list of relevant physico-chemical properties for different LNP compositions, based on ZP1, ZP2, ZP3, ZP4, ZP5, ZP6 and DMG-PEG is shown below in Table 6. 10 Table 6. Physico-chemical characteristics of LNPs In figure 1 (FIG. 1), the physicochemical properties (size and PDI) of the LNPs according to Example 2a are represented, measured via Zetasizer Nano (Malvern). Figure 2 (FIG.2) shows 15 a representation of mRNA encapsulation efficiency of LNPs according to Example 2a, measured via Ribogreen. The zetapotential of LNPs according to Example 2a, measured via Zetasizer Nano (Malvern), is represented in figure 3 (FIG. 3). In figure 4 (FIG. 4), the impact of LNPs according to Example 2a on the viability of the transfected HEK-293T cells is represented. Figure 5 (FIG.5) shows a representation of the Relative Mean Fluorescence Intensity (measured as 20 the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2a at mRNA concentration of 50 ng and 200 ng / well. Example 2b 25 LNPs were produced at a standard molar ratio ionizable lipid / DSPC / cholesterol / DMG-PEG2000 or stabilizing lipids prepared according to the examples disclosed herein, of about 50 / 10 / 38.5 / 1.5 (1.5%) or 48.5 / 10 / 38.5 / 3 (3%). As ionizable lipid, S-Ac7-DHDA was used, as reported by De Koker et al.4eGFP mRNA was encapsulated in all LNPs as reporter mRNA, at a mRNA / ionizable lipid molar ratio of 1 / 6. 30 A list of relevant physico-chemical properties for different LNP compositions, based on ZP3, -70- ZP5 and DMG-PEG is shown below in Table 7. Table 7. Physico-chemical characteristics of LNPs In figure 6 (FIG. 6), the physicochemical properties (size and PDI) of the LNPs according to 5 Example 2b are represented, measured via Zetasizer Nano (Malvern). Figure 7 (FIG.7) shows a representation of mRNA encapsulation efficiency of LNPs according to Example 2b, measured via Ribogreen. The zetapotential of LNPs according to Example 2b, measured via Zetasizer Nano (Malvern), is represented in figure 8 (FIG. 8). In figure 9 (FIG. 9), the impact of LNPs according to Example 2b on the viability of the transfected HEK-293T cells is represented. Figure 10 10 (FIG.10) shows a representation of the Relative Mean Fluorescence Intensity (measured as the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2b at mRNA concentration of 50 ng and 200 ng / well. 15 Example 2c LNPs were produced at a standard molar ratio ionizable lipid / DSPC / cholesterol / DMG-PEG2000 or PEG-alternative of about 50 / 10 / 38.5 / 1.5. S-Ac7-DHDA (IL1) was used as ionizable lipid. eGFP mRNA was encapsulated in all LNPs as reporter mRNA, at a mRNA / ionizable lipid molar ratio of 1 / 6. 20 A list of relevant physico-chemical properties for different LNP compositions, based on ZP8, ZP11, ZP14 and DMG-PEG is shown below in Table 8. -71- Table 8. Physico-chemical characteristics of LNPs In figure 11 (FIG.11), the physicochemical properties (size and PDI) of the LNPs according to Example 2c are represented, measured via Zetasizer Nano (Malvern). Figure 12 (FIG.12) shows 5 a representation of mRNA encapsulation efficiency of LNPs according to Example 2c, measured via Ribogreen. The zetapotential of LNPs according to Example 2c, measured via Zetasizer Nano (Malvern), is represented in figure 13 (FIG.13). In figure 14 (FIG.14), the effect of LNPs according to Example 2c on the viability of the transfected HEK-293T cells is represented. Figure 15 (FIG.15) shows a representation of the Relative Mean Fluorescence Intensity (measured as 10 the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2c at mRNA concentration of 50 ng and 200 ng / well. Example 2d 15 LNPs were produced at a standard molar ratio ionizable lipid / DSPC / cholesterol / DMG-PEG2000 or PEG-alternative of about 50 / 10 / 38.5 / 1.5 or 48.5 / 10 / 38.5 / 3. S-Ac7-DHDA (IL1) was used as ionizable lipid. eGFP mRNA was encapsulated in all LNPs as reporter mRNA, at a mRNA / ionizable lipid molar ratio of 1 / 6. A list of relevant physico-chemical properties for different LNP compositions, based on ZP8, 20 ZP11 and DMG-PEG is shown below in Table 9. Table 9. Physico-chemical characteristics of LNPs In figure 16 (FIG.16), the physicochemical properties (size and PDI) of the LNPs according to 25 Example 2d are represented, measured via Zetasizer Nano (Malvern). Figure 17 (FIG. 17) shows a representation of mRNA encapsulation efficiency of LNPs according to Example 2d, -72- measured via Ribogreen. The zetapotential of LNPs according to Example 2d, measured via Zetasizer Nano (Malvern), is represented in figure 18 (FIG.18). In figure 19 (FIG.19), the effect of LNPs according to Example 2d on the viability of the transfected HEK-293T cells is represented. Figure 20 (FIG. 20) shows a representation of the Relative Mean Fluorescence 5 Intensity (measured as the fold-increase in eGFP MFI compared to untreated cells) of eGFP expression in HEK-293T cells upon incubation with the indicated LNPs according to Example 2d at mRNA concentration of 50 ng and 200 ng / well. EXAMPLE 3: IN VIVO EXPERIMENTS 10 Example 3a: Bioluminescence imaging after IV administration of Fluc mRNA containing LNPs Materials and methods 15 Animals Mice were housed in IVC under specific pathogen–free conditions. All animal experiments were performed with approval from the Ethical Committee and animal care was according to established guidelines. Female Balb / C 6-weeks old (20-23g) were obtained from Charles River International Laboratories, Inc. (France) and housed (max 5 per cage) with free access to water 20 and standard laboratory animal chow. Intravenous injection For intravenous injection, mice are either placed in a warming chamber for vein dilation for no more than 10 min or the cage was placed under a red lamp for 10-20 min. When appropriately 25 warm, mice were restrained individually. The tail was swabbed with gauze dampened in 70% ethanol. The needle of a BD microfine syringe (20-25G) with LNP solution was carefully inserted into one of the side tail veins and applying slow pressure to the plunger a maximum volume of 200µL (for mice of 20-25g) was injected. The needle was removed from the vein and the local bleeding stopped by applying slight pressure to the puncture site with dry gauze. Animals were 30 subsequently observed for at least 10 minutes in their cage. Each injection was equivalent to 10 µg Fluc mRNA. Luminescence imaging Imaging was performed 24h after IV injection of LNP formulations. Each mouse was injected i.p. 35 with 100 μl D-luciferin (30 mg / mL,). Mice were then placed in an anesthesia induction chamber with oxygen supply (0.4-0.8 L / min) and isoflurane (5%) until they undergo narcosis. The flow of isoflurane was then reduced (3%) to maintain narcosis until mice are ready to be imaged. Mice are placed in a maximum of 3 per group in a stage inside the IVIS Lumina II (PerkinElmer) using the same anesthesia flow (3-4% Isoflurane). Imaging is performed with the parameters set to -73- Luminescence, auto exposure with background overlay and medium binning (4), using field of view D. Imaging of the animals was performed no longer than 15 min after luciferin injection (peak of the signal). Once in vivo images were taken, the mice were sacrificed by means of cervical dislocation, dissected and the liver was imaged. 5 mRNA synthesis FireFly luciferase (Fluc) mRNA was produced from a linearized peTheRNA vector using eTheRNA-optimized in vitro transcription (IVT) reaction conditions and purified via silica, cellulose. Uridine was fully substituted by N1-Methylpseudouridine (N1ѱ) to generate N1ѱ- 10 modified mRNA. LNP production Lipid based nanoparticles are produced by microfluidic mixing of an mRNA solution in sodium acetate buffer (100mM, pH4) and lipid solution in a 3:1 volume ratio at a speed of 12 mL / min or 15 20 mL / min using a T-junction device. The lipid solution contained of a mixture of the ionizable lipid of interest, DSPC (Avanti), Cholesterol (Sigma) and DMG-PEG2000 (Avanti) or stabilizing lipids prepared according to the examples disclosed herein. LNPs were produced at a standard molar ratio of ionizable lipid / DSPC / cholesterol / DMG-PEG2000 or stabilizing lipid of about 50 / 10 / 38.5 / 1.5. S-Ac7-DHDA (IL1) and MC3 (IL2) were used as ionizable lipid. Fluc mRNA was 20 encapsulated in all LNPs as reporter mRNA, at a mRNA / ionizable lipid molar ratio of 1 / 6. A list of relevant physico-chemical properties for different LNP compositions, based on ZP3, ZP5 and DMG-PEG is shown below in Table 10. 25 Table 10. Physico-chemical characteristics of LNPs Figure 21 (FIG.21) reveals the in vivo average radiance (normalized in function of photons / second / cm² / steradian) as captured by the IVIS. The mice are positioned in a manner that the image is taken in the supine view after 24h. Figure 22 (FIG. 22) reveals the ex vivo 30 average radiance (normalized in function of photons / second / cm² / steradian) of the liver, as captured by the IVIS. -74- Example 3b: Bioluminescence imaging after IV administration of Fluc mRNA containing LNPs LNP production 5 Lipid based nanoparticles are produced by microfluidic mixing of an mRNA solution in sodium acetate buffer (100mM, pH4) and lipid solution in a 3:1 volume ratio at a speed of 12 mL / min or 20 mL / min using a T-junction device. The lipid solution contained of a mixture of the ionizable lipid of interest, DSPC (Avanti), Cholesterol (Sigma) and DMG-PEG2000 (Avanti) or stabilizing lipids prepared according to the examples disclosed herein. LNPs were produced at a standard 10 molar ratio of ionizable lipid / DSPC / cholesterol / DMG-PEG2000 or stabilizing lipid of about 50 / 10 / 38.5 / 1.5 or at a molar ratio of ionizable lipid / DSPC / cholesterol / DMG-PEG2000 or stabilizing lipid of about 48.5 / 10 / 38.5 / 3. S-Ac7-DHDA (IL1) and MC3 (IL2) were used as ionizable lipid. Fluc mRNA was encapsulated in all LNPs as reporter mRNA, at a mRNA / ionizable lipid molar ratio of 1 / 6. 15 A list of relevant physico-chemical properties for different LNP compositions, based on ZP3, ZP5 and DMG-PEG is shown below in Table 11. Table 11. Physico-chemical characteristics of LNPs 20 Figure 23 (FIG.23) reveals the in vivo average radiance (normalized in function of photons / second / cm² / steradian) as captured by the IVIS. The mice are positioned in a manner that the image is taken in the supine view after 24h. 25 -75- Example 3c: hEPO expression of hEPO mRNA containing LNPs Materials and methods: 5 Animals Mice were housed in IVC under specific pathogen–free conditions. All animal experiments were performed with approval from the Ethical Committee for Animal Experiments and animal care was according to established guidelines. Female Balb / C 6-weeks old (20-23g) were obtained from Charles River International Laboratories, Inc. (France) and housed (max 5 per cage) with 10 free access to water and standard laboratory animal chow. Intravenous injection For intravenous injection, mice are either placed in a warming chamber for vein dilation for no more than 10 min or the cage was placed under a red lamp for 10-20 min. When appropriately 15 warm, mice were restrained individually. The tail was swabbed with gauze dampened in 70% ethanol. The needle of a BD microfine syringe (20-25G) with LNP solution was carefully inserted into one of the side tail veins and applying slow pressure to the plunger a maximum volume of 100µL (for mice of 20-25g) was injected. The needle was removed from the vein and the local bleeding stopped by applying slight pressure to the puncture site with dry gauze. Animals were 20 subsequently observed for at least 10 minutes in their cage. Each injection was equivalent to 5 µg hEPO mRNA.6h post injection, blood samples were taken and hEPO protein content was determined using a commercially available hEPO-ELISA kit according to the manufacturers protocol. 25 mRNA synthesis Human erythropoietin (hEPO) mRNA was produced from a linearized peTheRNA vector using eTheRNA-optimized in vitro transcription (IVT) reaction conditions and purified via silica, cellulose. Uridine was fully substituted by N1-Methylpseudouridine (N1ѱ) to generate N1ѱ- modified mRNA. 30 LNP production Lipid based nanoparticles are produced by T-mixing of an mRNA solution in sodium acetate buffer (100mM, pH4) and lipid solution in a 3:1 volume ratio at a speed of 12 mL / min or 20 mL / min. The lipid solution contained a mixture of the ionizable lipid of interest, DSPC (Avanti), 35 Cholesterol (Sigma) and DMG-PEG2000 (Avanti) or stabilizing lipid lipids prepared according to the examples disclosed herein. LNPs were dialyzed against TBS (10000 times more TBS volume than LNP volume) using slide-a-lyzer dialysis cassettes (20K MWCO, 3mL, ThermoFisher). Size, polydispersity and zeta potential were measured with a Zetasizer Nano (Malvern). mRNA encapsulation was measured by standard Ribogreen RNA assay (Invitrogen). -76- LNPs were produced at a standard molar ratio of ionizable lipid / DSPC / cholesterol / DMG- PEG2000 of about 50 / 10 / 38.5 / 1.5. S-Ac7-DHDA (IL1) and MC3 (IL2) were used as ionizable lipid. hEPO mRNA was encapsulated in all LNPs, at a mRNA / ionizable lipid molar ratio of 1 / 6. 5 A list of relevant physico-chemical properties for different LNP compositions, based on ZP5 and DMG-PEG is shown below in Table 12. Table 12. Physico-chemical characteristics of LNPs 10 Figure 24 (FIG.24) reveals the average hEPO conc in the blood 6h after IV injection, expressed as mU / mL EXAMPLE 4: IN VIVO EXPERIMENTS Example 4a: induction of anti-HA (hemagglutinin) immune responses upon intramuscular 15 mRNA vaccination Materials and methods Animals 20 Mice were housed in IVC under specific pathogen–free conditions. All animal experiments were performed with approval from the Ethical Committee for Animal Experiments and animal care was according to established guidelines. Female Balb / C 6-weeks old (20-23g) were obtained from Charles River International Laboratories, Inc. (France) and housed (max 5 per cage) with free access to water and standard laboratory animal chow. 25 Intramuscular injections and muscle thickness assessment All mice were housed under specific pathogen–free conditions, and animal studies were conducted under protocols and guidelines approved by the Ghent University animal care and use committee. Mice were injected in quadriceps muscle with mRNA LNPs in TBS (50 µl volume, 30 2 µg of mRNA) on 3 timepoints (day 0 prime, day 28 boost, day 56 second boost). Each mouse was injected 3 times using the same batch of LNP formulation. LNP formulations were stored at -80°C and monitored for their physico-chemical characteristics prior to their usage. The thickness of the muscle at the injection site was measured with an electronic external measuring -77- gauge (K220T, Kroeplin) at day 1 up to day 4 after injection. Assessment of mouse endpoint Immunoglobulin titers 100 µl of mouse whole blood was collected on day 0, day 28, day 56, day 70 and day 84 in 5 serum gel tubes (SarsTedt). Serum was separated from the blood clot by centrifugation at 10 000 g for 10 min at 4 °C. Black flat bottom maxisorp 96 well plates (437111, Life Technologies) were coated overnight at4 °C with 100 µl 1µg / ml of recombinant H1N1 (A / Puerto Rico / 8 / 1934) HA protein (Sino Biological, 11684-V08H) in carbonate / bicarbonate buffer (0.1 M, pH 9.6). Plates were subsequently blocked with 100 µl of 3%BSA (05479-250g, Sigma) in PBS (w / v) for 10 2h. Subsequently, plates were washed 3 times with PBS / 0.1%Tween (10113103, Fisher Scientific). A serial dilution of serum samples was added to the plates (initial 100X dilution of serum for d21 and initial 5000x serum dilution for d35 and d70; 5X dilution steps). After 2h incubation at RT 15 plates were washed 5 times and solutions of rabbit anti-mouse IgG1 conjugated with HRP (1:15 000, Biorad, OBT1508P) or goat anti-mouse IgG2a conjugated with HRP (1:8000, STAR133P Biorad) were added for another 1h. After a final wash, the fluorescent Amplex UltraRed Reagent (A36006,Invitrogen) was used to develop plates according to the manufacturers’ instructions. Plates were read on a Tecan Infinite 200 Pro with λex=540nm, λem=590nm. The dilutions of 20 serum of TBS treated mice served for cut-off determination, being the average fluorescence measured in the TBS samples plus 3 standard deviations. All points beyond cut-off were considered to be below quantification limit. The curves were fitted with a 5PL algorithm in (Prism) to the dilution data then the endpoint titer was calculated at cross point of the modeled curve with the cut-off. 25 Assessment of serum cytokines titers by LegendPlex Blood collected 6 h post injection was used to check for inflammatory cytokines by means of LegendplexTM (Biolegend) with a custom made pre-mixed cytokine panel (900001482), including IFNb, IFNg and CXCL9. Cytokines were assessed, according to manufacturing instructions. Fluorescence was measured by Flow Cytometry (AtuneNxt flow cytometer, 30 ThermoFisher, A29003) using the APC channel (for bead populations) and the PE channel (antibody binding intensity) with a pre-defined template for bead population gating. The data was collected and analyzed using the Legendplex Qognit tool (https: / / legendplex.qognit.com / ) mRNA synthesis 35 Hemagglutinin (HA) mRNA was produced from a linearized peTheRNA vector using eTheRNA- optimized in vitro transcription (IVT) reaction conditions and purified via silica, cellulose. Uridine was fully substituted by N1-Methylpseudouridine (N1ѱ) to generate N1ѱ-modified mRNA. -78- LNP production LNP formulations were prepared as indicated above. LNPs were frozen at -80°C using 8% sucrose as cryoprotectant. S-Ac7-DHDA (IL1) and SM-102 (IL3) were used as ionizable lipid. HA mRNA was encapsulated in all LNPs. All formulations were prepared in a sterile manner with 5 a N / P ratio of 10, except for SM-102 bearing LNPs where an N / P ratio of 6 was used. All formulations were characterized for size and PDI using Dynamic Light Scattering Zetasizer Nano-ZS (Malvern Pan analytical Ltd., Malvern, UK) and stored afterwards at -80°C. Prior to each injection, physico-chemical properties and mRNA encapsulation efficiencies were measured. The physico-chemical characteristics of the formulations, based on ZP5 and DMG- 10 PEG, at each injection timepoint can be found in Table 13. Table 13. List of relevant physico-chemical properties of different LNP formulations. Figure 25 (FIG.25) reveals the IgG1 titers at day 56 as determined by ELISA and expressed as 15 the reciprocate of the dilution of the sera that provides signal that is at least 3 times higher than the background ± 3SD. Figure 26 (FIG.26) reveals the IgG2a titers at day 56 as determined by ELISA and expressed as the reciprocate of the dilution of the sera that provides signal that is at least 3 times higher than the background ± 3SD. Figure 27 (FIG.27) reveals the expression of IFNb as determined by LegendPlex 6 h post boost injection at day 56. Figure 28 (FIG. 28) 20 reveals the expression of IFNq as determined by LegendPlex 6 h post boost injection at day 56 Figure 29 (FIG. 29) reveals the expression of CXLC9 as determined by LegendPlex 6 h post boost injection at day 56 -79- EXAMPLE 5: LONG TERM LNP STABILITY The lipid nanoparticles (LNPs) described in Table 12 were subjected to long-term stability testing at 4^°C. At predetermined intervals (1 week, 2 weeks, 3 weeks, 1 month, 3 months, and 6 months), test vials were withdrawn from refrigerated storage and equilibrated to room 5 temperature prior to analysis. At each timepoint, the physicochemical properties, including particle size and PDI, as well as the mRNA encapsulation efficiency, were measured. Figure 30 (FIG.30) and figure 31 (FIG 31) illustrate the physicochemical properties (particle size and PDI) of the LNP formulations at each timepoint, as measured using a Zetasizer Nano 10 (Malvern). LNPs formulated with ZP5 as the stabilizing lipid exhibited stable size and PDI profiles over 6 months of storage at 4^°C. In contrast, LNPs containing DMG-PEG demonstrated a gradual increase in particle size and PDI over the same period. Figure 32 (FIG.32) presents the mRNA encapsulation efficiency of the LNPs at each timepoint, as determined using the Ribogreen assay. ZP5-containing LNPs maintained consistent encapsulation efficiency 15 throughout the 6-month storage period, whereas DMG-PEG LNPs showed a gradual decrease. REFERENCES 1. Vanparijs et al. Polymer-protein conjugation via a ‘grafting to’ approach – a comparative 20 study of the performance of protein-reactive RAFT chain transfer agents Polym. Chem. 2015, 6, 5602–5614 2. Uvyn et al. Efficient Innate Immune Killing of Cancer Cells Triggered by Cell-Surface Anchoring of Multivalent Antibody-Recruiting Polymers Angew. Chem.2019, 131, 13122- 13127 25 3. Jesson et al. H2O2 Enables Convenient Removal of RAFT End-Groups from Block Copolymer Nano-Objects Prepared via Polymerization-Induced Self-Assembly in Water Macromolecules 2017, 50, 182−191 4. De Koker et al. WO2022136641 30

Claims

-80- CLAIMS 1. A stabilizing lipid represented by formula (I)5 wherein n is an integer from 2 to 100; m is 0, or an integer selected from 1 to 100; R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more 10 heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each 15 of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; 20 each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further 25 comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally-81- and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; 5 Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising 10 one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl.

2. A stabilizing lipid as defined in claim 1 and represented by formula (I)15 wherein n is an integer from 2 to 100; m is 0; R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - 20 C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from -C(O)NR2-, -OC(O)NR2-, and -C(O)O-; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each 25 of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and-82- -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; 5 each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, and -C1-12alkylene-; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is10 optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, and -SH; Z is selected from -Ph, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, and -Ph; and 15 Y2’ is selected from -H, and -C1-6alkyl.

3. A stabilizing lipid as defined in claim 1, and represented by formula (II)20 wherein n is an integer from 2 to 100; m is 0, or an integer selected from 1 to 100; R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more 25 heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each-83- of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; 5 the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein 10 each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is15 optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; 20 Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1and Ar2are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. 25 4. A stabilizing lipid as defined in any one of claims 1 to 2, and represented by formula (III)-84- wherein n is an integer from 2 to 100; m is 0, or an integer selected from 1 to 100; 5 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each 10 of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; 15 each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X and X’ are each independently selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further 20 comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - 25 O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; 30 R2’is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. 35 5. A stabilizing lipid as defined in any one of claims 1 to 2, and represented by formula (IV)-85-wherein n is an integer from 2 to 100; 5 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, -OC(O)NR2-, - 10 OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and 15 -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X is selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl; 20 L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally 25 and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl;-86- Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; 5 R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl. 10 6. A stabilizing lipid as defined in any one of claims 1 to 2, and represented by formula (V)wherein n is an integer from 2 to 100; 15 R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4; R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each 20 of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; 25 each instance of R3 and each instance of R3’ is independently selected from -H, and -CH3; X is selected from -O-, and -NH-; each instance of R6 is independently selected from -H, -C1-12alkyl, and -C2-12alkenyl;-87- L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, -C2-20alkenyl 5 and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, - O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and -OC(O)-C2-20alkenyl; Y1 is selected from -SC(S)Z, -H, -OH, -SH, -I, -SNO, and -C=CH2; 10 Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1 and Ar2 are each independently a 5- to 6-membered aromatic cycle optionally comprising 15 one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and -C1-6alkyl.

7. A stabilizing lipid as defined in any one of claims 1 to 6, wherein Y2 is -CN, and Y2’ is -CH3; or wherein Y2 is -H, and Y2’ is -CH3. 20 8. A stabilizing lipid as defined in any one of claims 1 to 6, wherein n is an integer from 3 to 50, preferably from 4 to 45, more preferably from 5 to 40, even more preferably from 10 to 30.

9. A stabilizing lipid as defined in claim 1 and being selected from the list comprising: 25-93-wherein n and m are as defined in any one of preceding claims.

10. Method to prepare a lipid, in particular a stabilizing lipid, said method comprising the steps 5 of: a) providing first monomers comprising a zwitterionic moiety, in particular a phosphorylcholine moiety, represented by formula (VII)-94-wherein R3 is independently selected from -H, and -CH3; and 5 X is selected from -O-, and -NH-; b) optionally providing one or more further monomers represented by formula (VIII)wherein 10 R3’is independently selected from -H, and -CH3; and X’ is selected from -O-, and -NH-; c) providing an initiator, in particular a radical initiator; d) providing a RAFT agent represented by formula (IX)15 wherein R1 is selected from -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1- 20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently 20 substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R4, and -C(O)O-R4;-95- Q is selected from a direct bond, -O-, -OC(O)-, -C(O)O-, -OC(O)O-, -C(O)NR2-, - OC(O)NR2-, -OC(S)NR2-, -SC(O)NR2-, and -NR2C(O)NR2-; each instance of R2 is independently selected from -H, -C1-20alkyl, -C2-20alkenyl and -C2- 20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2-20alkynyl optionally and 5 independently comprises one or more heteroatoms selected from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents independently selected from -OH, -OC(O)-R5, and -C(O)O-R5; the total number of C atoms in R1, and R2 together is at least 8; L1 is selected from a direct bond, -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene; 10 wherein each of said -C1-12alkylene-, -C2-12alkenylene, and -C2-12alkynylene optionally further comprises one or more heteroatoms selected from N, O and S; each instance of R4 and each instance R5 is independently selected from -C1-20alkyl, - C2-20alkenyl and -C2-20alkynyl; wherein each of said -C1-20alkyl, -C2-20alkenyl and -C2- 20alkynyl optionally and independently comprises one or more heteroatoms selected 15 from O, N and S and / or is optionally and independently substituted with from 1 to 3 substituents selected from -OH, -O-C1-20alkyl, -O-C2-20alkenyl, -OC(O)-C1-20alkyl, and - OC(O)-C2-20alkenyl; Z is selected from -Ar2, -Bn, and -S-C1-12alkyl; Y2 is selected from -H, -CN, -Ar1, and -C(O)O-R2’; 20 Y2’ is selected from -H, and -C1-6alkyl; R2’ is -C1-20alkyl; and Ar1and Ar2are each independently a 5- to 6-membered aromatic cycle optionally comprising one or more heteroatoms selected from N, O and S and / or are optionally and independently substituted with from 1 to 3 substituents selected from -halo, and - 25 C1-6alkyl; and e) performing reversible addition–fragmentation chain transfer (RAFT) polymerization by heating a mixture of the first monomers, optionally the one or more further monomers, the initiator, and the RAFT agent, thereby providing the stabilizing lipid. 30 11. A nanoparticle or nanoparticle composition comprising a stabilizing lipid as defined in any one of claims 1 to 9, or a stabilizing lipid prepared according to the method as defined in claim 10.

12. The nanoparticle or nanoparticle composition according to claim 11, further comprising an 35 ionizable lipid, a helper lipid and / or a sterol.

13. The nanoparticle or nanoparticle composition according to any one of claims 11 to 12, further comprising an active agent, in particular a nucleic acid, preferably mRNA.-96- 14. Use of a stabilizing lipid as defined in any one of claims 1 to 9, or a stabilizing lipid prepared according to the method as defined in claim 10, in the manufacture of a nanoparticle or nanoparticle composition. 5 15. A pharmaceutical composition comprising a nanoparticle or nanoparticle composition as defined in any one of claims 11 to 13, and a pharmaceutically acceptable agent.

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