APOE lipoprotein system

Abstract

The present disclosure includes lipoprotein-based systems and compositions. The lipoprotein system may optionally comprise a payload for delivery to cells, tissues, organs, and / or a subject in need thereof. Also provided herein are methods of utilizing lipoprotein systems.

Description

Background Art

[0001] Lipoproteins are complex molecular assemblies that are key players in the intracellular and / or extracellular lipid metabolism cascade. Lipids play important biological roles as structural components of cell membranes, energy reservoirs, and mediators of key signaling events. For example, brain lipids play a role in membrane formation, synaptogenesis, neurogenesis, and impulse conduction. Regulating lipids has potential utility in controlling or preventing diseases (acute or chronic), syndromes, injuries, and / or conferring protective effects. There is an urgent need for compositions that can regulate lipid metabolism, lipid transport, and / or effectively deliver bioactive lipids.

[0002] Effective in vivo delivery of agents such as small molecules, proteins, peptides, nucleic acids, and other biomolecules represents an ongoing clinical challenge. The characteristics of lipoproteins make them attractive candidates for use as molecular transporters. The present disclosure provides a lipoprotein system that represents a versatile platform that can be manipulated and tailored for specific applications. Summary of the Invention

[0003] The present disclosure provides a lipoprotein system comprising apolipoprotein and lipids (e.g., glycerophospholipids). Apolipoprotein is well-known for its ability to bind lipid molecules and cross the blood-brain barrier. The system disclosed herein utilizes this feature of apolipoprotein to design particles (e.g., nanoparticles), which are optionally bound to a payload, can regulate lipid metabolism and deliver the payload directly to the brain. Particles disclosed herein can be formulated into various shapes, e.g., discs. The lipoprotein system disclosed herein can be used to treat diseases or conditions (e.g., diseases of the nervous system, autoimmune diseases, cardiovascular diseases, vascular diseases, respiratory diseases, metabolic diseases, gastrointestinal diseases, genetic syndromes, cancer or multi-system diseases, etc.).

[0004] The present disclosure exploits the unprecedented discovery of the biophysical advantages of lipoprotein systems comprising apolipoproteins, such as apolipoprotein E (APOE), and glycerophospholipids, such as phosphatidylglycerol (PG). The incorporation of glycerophospholipids, such as PG lipids, imparts to the lipoprotein systems of the present disclosure improved polydispersity, thermal stability, and binding affinity compared to other lipoprotein systems. In addition, the present disclosure provides novel peptide sequences for use in such lipoprotein systems. The novel polypeptide sequences comprise a feature-by-feature assembly of the sequences disclosed herein to produce functional polypeptide sequences for use in the present invention. The present disclosure provides lipoprotein systems of varying sizes, shapes, dimensions, lipid compositions, and / or apolipoprotein content that exhibit beneficial biophysical properties.

[0005] In one aspect, the present disclosure provides a lipoprotein system comprising: (a) APOE; and (b) a lipid; wherein the lipid is operably associated with APOE. In some embodiments, APOE comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 267-385. In some embodiments, APOE comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 267-385. In some embodiments, APOE comprises an amino acid sequence that is any one of SEQ ID NOs: 267-385. In some embodiments, the APOE comprises one or more mutations relative to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 268, wherein the one or more mutations are selected from the group consisting of A6T (SEQ ID NO: 388), A7V (SEQ ID NO: 389), L9P (SEQ ID NO: 390), V10I (SEQ ID NO: 391), T11A (SEQ ID NO: 392), T11S (SEQ ID NO: 393), F12Y (SEQ ID NO: 394), F12L (SEQ ID NO: 395), L13R (SEQ ID NO: 396), A18P (SEQ ID NO: 397), A18T (SEQ ID NO: 398), E21K (SEQ ID NO: 399), A23V (SEQ ID NO: 400), V24L (SEQ ID NO: 401), T26_E29dup (SEQ ID NO: 402), P28L (SEQ ID NO: 403), NO:403), E31K (SEQ ID NO:404), R33C (SEQ ID NO:405), R33H (SEQ ID NO:406), Q35R (SEQ ID NO:407), E37K (SEQ ID NO:408), Q39R (SEQ ID NO:409), G41S (SEQ IDNO:410), R43del (SEQ ID NO:411), R43C (SEQ ID NO:412), R43H (SEQ ID NO:413), L46P (SEQ ID NO:415), L48V (SEQ ID NO:416), R50C (SEQ ID NO:417), R50S (SEQ ID NO:418), R50G (SEQ ID NO:419), R50P (SEQ ID NO:420), R50H (SEQ ID NO:421), R50L (SEQ ID NO:422), R56H (SEQ ID NO:423), T60A (SEQ IDNO:424)、Q64H(SEQ ID NO:425)、E68del(SEQID NO:426)、E68V(SEQ ID NO:428)、E68D(SEQ ID NO:429)、L69Q(SEQ ID NO:430)、L69P(SEQ ID NO:431)、L70F(SEQ ID NO:432)、Q73R(SEQ ID NO:433)、V74A(SEQ ID NO:434)、Q76R(SEQ ID NO:435)、E77K(SEQ ID NO:436)、A80E(SEQ ID NO:437)、M82R(SEQ ID NO:438)、D83E(SEQ ID NO:439)、E84K(SEQ ID NO:440)、M86V(SEQ ID NO:441)、E88Q(SEQ IDNO:442)、L89S(SEQ ID NO:443)、K90E(SEQ ID NO:444)、K90N(SEQ ID NO:445)、Y92C(SEQID NO:446)、K93fs(SEQ ID NO:447)、K93T(SEQ ID NO:448)、K93R(SEQ ID NO:449)、K93N(SEQ ID NO:450)、S94*(SEQ ID NO:451)、Q99K(SEQ ID NO:452)、Q99R(SEQ ID NO:453)、P102R(SEQ ID NO:454)、V103L(SEQ ID NO:455)、V103L(SEQ ID NO:456)、A104T(SEQ IDNO:457)、E106Q(SEQ ID NO:458)、R108_A118dup(SEQ ID NO:459)、R108Q(SEQ ID NO:460)、R110fs(SEQ ID NO:461)、R110Q(SEQ ID NO:461)、S112Y(SEQ ID NO:462)、K113E(SEQ ID NO:463)、E114K(SEQ ID NO:464)、L115R(SEQ ID NO:465)、A117V(SEQ ID NO:466)、Q119P(SEQ ID NO:467)、A120S(SEQ ID NO:468)、A120D(SEQ ID NO:469)、R121W(SEQID NO:470)、G123R(SEQ ID NO:471)、D128N(SEQ IDNO:472)、V129M(SEQ ID NO:473)、G131C(SEQ ID NO:474)、R132C(SEQ ID NO:475)、R132L(SEQ ID NO:476)、Q135R(SEQ IDNO:477)、Y136C(SEQ ID NO:478)、R137C(SEQ ID NO:479)、R137G(SEQ ID NO:480)、R137H(SEQ ID NO:481)、G138C(SEQ ID NO:482)、V140L(SEQ ID NO:483)、V140M(SEQ ID NO:484)、L144I(SEQ ID NO:485)、G145R(SEQ ID NO:486)、G145S(SEQ ID NO:487)、G145D(SEQID NO:488)、G145A(SEQ ID NO:489)、Q146*(SEQ ID NO:490)、L151M(SEQ ID NO:491)、R152W(SEQ ID NO:492)、R152Q(SEQ ID NO:493)、V153M(SEQ ID NO:494)、R154S(SEQ IDNO:330)、R154fs(SEQ ID NO:495)、R154C(SEQ ID NO:496)、R154L(SEQ ID NO:497)、S157F(SEQ ID NO:498)、L159P(SEQ ID NO:499)、R160G(SEQ ID NO:500)、163C(SEQ ID NO:501)、R163H(SEQ ID NO:502)、K164Q(SEQ ID NO:503)、L167del(SEQ ID NO:504)、R168H(SEQ ID NO:505)、D169Y(SEQ ID NO:506)、D172N(SEQ ID NO:507)、Q174K(SEQ ID NO:508)、V179A(SEQ ID NO:509)、Y180H(SEQ ID NO:510)、Q181E(SEQ ID NO:511)、Q181H(SEQID NO:512)、A184S(SEQ ID NO:513)、G187A(SEQ ID NO:514)、G187V(SEQ ID NO:515)、G191_R198dup(SEQ ID NO:516)、E189K(SEQ ID NO:517)、R190C(SEQ IDNO:518)、G191S(SEQ ID NO:519)、S193R(SEQ ID NO:520)、R196C(SEQ ID NO:521)、R198C(SEQ ID NO:522)、G200R(SEQ ID NO:523)、R207S(SEQ ID NO:524)、R207C(SEQ ID NO:525)、R207H(SEQID NO:526)、R207P(SEQ ID NO:527)、V208L(SEQ ID NO:528)、V208M(SEQ ID NO:529)、V213G(SEQ ID NO:530)、G214S(SEQ ID NO:531)、G218R(SEQ ID NO:532)、G218S(SEQ IDNO:533)、Q219E(SEQ ID NO:534)、P220L(SEQ ID NO:535)、L221P(SEQ ID NO:536)、Q222*(SEQ ID NO:537)、Q222K(SEQ ID NO:538)、Q222R(SEQ ID NO:539)、R224P(SEQ ID NO:540)、R224L(SEQ ID NO:541)、A225T(SEQ ID NO:542)、A227S(SEQ ID NO:543)、W228*(SEQID NO:544)、G229R(SEQ ID NO:545)、G229V(SEQ ID NO:546)、E230K(SEQ ID NO:547)、R231Q(SEQ ID NO:548)、A234T(SEQ ID NO:549)、A234V(SEQ ID NO:550)、R235W(SEQ IDNO:551)、R235Q(SEQ ID NO:552)、E238del(SEQ ID NO:553)、E238D(SEQ ID NO:554)、M239I(SEQ ID NO:555)、G240R(SEQ ID NO:556)、S241R(SEQ ID NO:557)、T243fs(SEQ IDNO:558)、R242W(SEQ ID NO:559)、R242G(SEQ ID NO:560)、R242P(SEQ ID NO:561)、T243N(SEQ ID NO:562)、R246S(SEQ ID NO:563)、R246C(SEQ ID NO:564)、R246P(SEQ IDNO:565)、D248E(SEQ ID NO:566)、E249K(SEQ ID NO:567)、E249Q(SEQ ID NO:568)、E256V(SEQID NO:569)、R258H(SEQ ID NO:570)、A259P(SEQ ID NO:571)、E262K(SEQ ID NO:572)、E263K(SEQ ID NO:573)、Q267R(SEQ ID NO:574)、V254E(SEQ ID NO:331)、R269fs(SEQ IDNO:575)、R269C(SEQ ID NO:576)、R269G(SEQ ID NO:577)、E273G(SEQ ID NO:578)、A274G(SEQ ID NO:579)、Q276*(SEQ ID NO:580)、A277V(SEQ ID NO:581)、R278C(SEQ ID NO:582)、L279fs(SEQ ID NO:583)、W282C(SEQ ID NO:584)、E284G(SEQ ID NO:585)、E284D(SEQ ID NO:586)、L286M(SEQ ID NO:587)、V287M(SEQ ID NO:588)、D289A (SEQ ID NO:589)、R292C(SEQ ID NO:590)、R292H(SEQ ID NO:591)、W294C(SEQ ID NO:592)、A295T(SEQID NO:593)、G296R(SEQ ID NO:594)、G296W(SEQ ID NO:595)、L297P(SEQ ID NO:596)、E299Q(SEQ ID NO:597)、K300R(SEQ ID NO:598)、K300N(SEQ ID NO:599)、V301L(SEQ IDNO:600)、A303S(SEQ ID NO:601)、V305M(SEQ ID NO:602)、T307I(SEQ ID NO:603)、A309T(SEQ ID NO:604)、P311A(SEQ ID NO:605)、S314R(SEQ ID NO:606)、*318ext(SEQ ID NO:607)、W38*(SEQ ID NO:608)、E98fs(SEQ ID NO:609)、A117T(SEQ ID NO:610)、L122M(SEQIDIn some embodiments, the one or more mutations comprise R154S. In some embodiments, the one or more mutations comprise V254E. In some embodiments, APOE comprises any one of SEQ ID NOs: 275-277.

[0006] In some embodiments, APOE comprises one or more sequence regions selected from signal sequence, N-terminal region, structured sequence region, hinge region, joint region and C-terminal region. In some embodiments, APOE comprises more than one structured sequence region. In some embodiments, each structured sequence region is selected from alpha helical sequence region, beta conformation (beta confirmation) sequence region and beta turn sequence region.

[0007] In some embodiments, APOE comprises one or more chemical modifications. In some embodiments, the one or more chemical modifications include one or more post-translational modifications (PTMs). In some embodiments, the one or more post-translational modifications are selected from the group consisting of oxidation, carbamylation, oxidation-carbamylation, acetylation, phosphorylation, ubiquitination, biotinylation, carboxylation, deamidation, deamination, deacetylation, dihydroxylation, dephosphorylation, formylation, γ-carboxyglutamate, glutathionylation, saccharification, hydroxylation, methylation, nitration, sumoylation, N-transglutamination or O-transglutamination, glycosylation, and farnesylation.

[0008] In some embodiments, APOE includes an oxidatively coupled dimer comprising two APOE monomers. In some embodiments, the APOE monomer comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 267-385. In some embodiments, the APOE monomer comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 267-385. In some embodiments, the APOE monomer is any one of SEQ ID NOs: 267-385. In some embodiments, the monomer is any one of SEQ ID NOs: 268, 271, 275-277, or 294.

[0009] In some embodiments, the lipid comprises formula (I):

[0010]

[0011] in:

[0012] X 1 and X 2 are independently N, O or absent;

[0013] R 1 and R 2 is independently optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, or absent; and

[0014] R 3 Selected from:

[0015]

[0016] In some embodiments, the lipid is a glycerophospholipid. In some embodiments, the lipid is a lysolipid.

[0017] In some embodiments, the lipid is a phosphatidylglycerol. In some embodiments, the phosphatidylglycerol is 1-palmitoyl-2-oleoyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (POPG), 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) or 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG).

[0018] In some embodiments, the lipid is a phosphatidylcholine. In some embodiments, the phosphatidylcholine is 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or N-oleoyl-D-erythro-sphingosylphosphorylcholine (18:1SM).

[0019] In some embodiments, the lipid is phosphatidylserine. In some embodiments, the phosphatidylserine is 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS), or 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS).

[0020] In some embodiments, lipid comprises at least 2 kinds of unique lipids.In some embodiments, described at least two kinds of unique lipids comprise a first lipid and a second lipid.In some embodiments, the molar ratio of the first lipid to the second lipid is about 1:100 first lipid: second lipid to about 100:1 first lipid: second lipid.In some embodiments, the molar ratio of the first lipid to the second lipid is about 1:1 first lipid: second lipid.In some embodiments, the first lipid is POPC, and the second lipid is POPS.

[0021] In some embodiments, the molar ratio of APOE to lipid is from 1:10,000 APOE:lipid to 1:1 APOE:lipid. In some embodiments, the molar ratio of APOE to lipid is from 1:500 APOE:lipid to 1:30 APOE:lipid. In some embodiments, the molar ratio of APOE to lipid is from 1:200 APOE:lipid to 1:50 APOE:lipid. In some embodiments, the molar ratio of APOE to lipid is from 1:100 APOE:lipid.

[0022] In some embodiments, the system has a disc-like, spherical, cylindrical, lamellar, or elliptical form. In some embodiments, the system has a disc-like form. In some embodiments, the diameter of the system is 1 nm to 100 nm. In some embodiments, the system has a polydispersity of at most 25%. In some embodiments, the system has a polydispersity of at most 20%. In some embodiments, the system has a polydispersity of at most 15%. In some embodiments, the system has a polydispersity of at most 10%. In some embodiments, the system has a polydispersity of at most 5%.

[0023] In some embodiments, the lipoprotein system further comprises a payload. In some embodiments, the payload is selected from the group consisting of a peptide payload, a protein payload, a nucleic acid payload, a lipid payload, a lipid derivative payload, a carbohydrate payload, a glycolipid payload, a metabolite payload, a metabolite derivative payload, and a small molecule payload.

[0024] In some embodiments, the payload is a small molecule payload. In some embodiments, the small molecule is selected from the group consisting of antioxidants, antitumor agents, analgesics, anesthetics, antibacterial agents, anticonvulsants, antidementia agents, antidepressants, antiemetics, antifungals, antigout agents, anti-inflammatory agents, antimigraine agents, myasthenic agents, antimycobacterial agents, antiparasitic agents, antiparkinsonian agents, antipsychotic agents, anticonvulsants, antivirals, antianxiety agents, bipolar disorder agents, blood glucose regulators, blood products, blood modifiers, blood volume expanders, chemotherapeutic agents, cardiovascular agents, central nervous system agents, dental oral agents, dermatological agents, electrolytes, enzyme replacement agents, enzyme modifiers, gastrointestinal agents, genitourinary agents, immune agents, inflammatory bowel disease agents, metabolic bone disease agents, ophthalmic agents, otic agents, respiratory agents, sedatives, hypnotic agents, and skeletal muscle relaxants.

[0025] In some embodiments, the payload is a nucleic acid. In some embodiments, the nucleic acid is RNA, DNA, or cDNA. In some embodiments, the RNA is mRNA, siRNA, microRNA, interfering RNA, replicon mRNA, guide RNA, short hairpin RNA (shRNA), piwi interacting RNA (piRNA), non-coding RNA (ncRNA), long non-coding RNA (lncRNA), double-stranded RNA (dsRNA), single-stranded RNA, or circular RNA (circRNA).

[0026] In some embodiments, the nucleic acid is an antisense oligonucleotide (ASO).In some embodiments, the antisense oligonucleotide can be modified (e.g., having a modification in the ribose moiety of the nucleoside or in the internucleoside linkage).

[0027] In some embodiments, the lipoprotein system further comprises a lipoprotein system modifier. In some embodiments, the lipoprotein system modifier is a targeting agent, a regulating agent, a solubilizing agent, a stabilizing agent, or a detecting agent.

[0028] On the other hand, present disclosure provides the method for treating or preventing the disease or illness of subject, and described method includes administering lipoprotein system as described herein.In some embodiments, disease, injury or illness are nervous system disease, autoimmune disease, cardiovascular disease, vascular disease, respiratory disease, metabolic disease, gastrointestinal disease, genetic syndrome, cancer or multi-system disease.In some embodiments, disease, injury or illness are nervous system disease.In some embodiments, disease, injury or illness are selected from following one or more: degenerative cervical spondylosis, Niemann-Pick disease (Niemann-Pickdisease), amyotrophic lateral sclerosis (ALS), multiple sclerosis, Parkinson's disease (Parkinson's disease), Alzheimer's disease (Alzheimer's disease), Huntington's disease (Huntington's disease), Smith-Lemli Opitz syndrome (Smith-Lemli Opitz syndrome, SLOS), multiple system atrophy, prion disease, cognitive impairment or dementia.In some embodiments, nervous system disease is Niemann-Pick disease. In some embodiments, the neurological disease is Alzheimer's disease. In some embodiments, the neurological disease is severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection, or a neurological disease caused by SARS CoV-2 infection.

[0029] definition

[0030] As used herein, the term "apolipoprotein" and its abbreviation "APO" refer to a protein that is associated with and / or capable of interacting with a lipid.

[0031] As used herein, the term "apolipoprotein E" or the abbreviation "APOE" refers to any apolipoprotein E, including fragments and variants thereof.

[0032] As used herein, the term "apolipoprotein variant" refers to apolipoprotein polypeptide or polynucleotide that is different from other forms of apolipoprotein polypeptide or polynucleotide in some aspects or is different from the form or type of apolipoprotein polypeptide or polynucleotide reference standard. Such apolipoprotein polypeptide or polynucleotide reference standard can be a parent apolipoprotein polypeptide or polynucleotide, or a starting apolipoprotein polypeptide or polynucleotide that has differences in structure, sequence or function, and these differences distinguish apolipoprotein variant from starting or reference standard. As used herein, apolipoprotein variant also includes apolipoprotein mutations, which can include amino acid substitutions, deletions, insertions, and amino acid sequence changes (e.g., reverse sequences, scrambled sequences, multidomain sequences, switch domain sequences). As used herein, apolipoprotein variants also include fusion polypeptides.

[0033] As used herein, the term "alpha-helical sequence region" refers to a type of structure in which the polypeptide backbone is tightly wound around an imaginary axis drawn longitudinally through the middle, with the R groups of the amino acids projecting outward from the backbone. In this conformation, each backbone NH group forms a hydrogen bond with the backbone C=O groups of the amino acids located in the first four residues in the protein sequence.

[0034] As used herein, the term "β conformation sequence region" refers to a type of structure in which the polypeptide backbone extends in a zigzag pattern rather than a helical structure. In some embodiments, the zigzag polypeptide chains can be arranged side by side to form a β sheet.

[0035] As used herein, the term "beta turn region" refers to a type of structure that connects the ends of two adjacent segments of a beta sheet.

[0036] As used herein, the term "derivative" refers to a form or version of a compound that differs from the parent compound by at least one atom or group.

[0037] As used herein, the term "fatty acid" refers to a carboxylic acid having a long-chain hydrocarbon side group.

[0038] As used herein, in the context of polypeptides, the term "fragment" refers to a contiguous stretch of amino acids in the linear sequence of a polypeptide.

[0039] As used herein, the term "isolated" means separated from cellular components and other components with which a polynucleotide, polypeptide, protein, or fragment thereof is normally associated in nature. For example, with respect to polypeptides, an isolated polypeptide is one that is separated from the amino and carboxyl termini with which it is normally associated in a naturally occurring sequence. It will be apparent to those skilled in the art that a non-naturally occurring polynucleotide, polypeptide, protein, or fragment thereof does not require "isolation" to distinguish it from its naturally occurring counterpart. In addition, a "concentrated," "separated," or "diluted" polynucleotide, polypeptide, protein, or fragment thereof is distinguished from its naturally occurring counterpart in that it is "concentrated" to a greater extent than its naturally occurring counterpart in terms of concentration or number of molecules per unit volume, or "separated" or "diluted" to a lesser extent than its naturally occurring counterpart. A polynucleotide, polypeptide, protein, or fragment thereof that differs from its naturally occurring counterpart in primary sequence or, for example, glycosylation pattern, need not be present in its isolated form, as it can be distinguished from its naturally occurring counterpart by its primary sequence or, alternatively, by another characteristic, such as glycosylation pattern. Thus, a non-naturally occurring polypeptide is provided as an embodiment distinct from an isolated naturally occurring polypeptide. Proteins produced in bacterial cells are provided as a distinct embodiment from naturally occurring proteins isolated from the eukaryotic cells in which they are naturally produced.

[0040] As used herein, the term "lipoprotein system" refers to a biochemical assembly comprising one or more apolipoproteins and one or more lipids.

[0041] As used herein, the term "lipoprotein system modifier" refers to any macromolecule or small molecule that can alter / modulate the location, structure, function, solubility, detection, synthesis, assembly and / or degradation of the lipoprotein system in vitro, ex vivo or in vivo.

[0042] As used herein, the term "lipid" refers to a molecule of biological origin that is soluble in organic solvents (eg, chloroform) but has little solubility in water.

[0043] As used herein, the term "nucleic acid" refers to an RNA molecule or a DNA molecule composed of a ribonucleotide chain or a deoxyribonucleotide chain, respectively. In addition, as used herein, "nucleic acid" includes any compound or substance containing a nucleotide polymer (e.g., linked nucleosides). Such polymers may be referred to as polynucleotides.

[0044] As used herein, the term "nucleoside" refers to a molecule composed of a heterocyclic base and its sugar.

[0045] As used herein, the term "nucleotide" refers to a nucleoside having a phosphate group or variants thereof on its 3' or 5' sugar hydroxyl group. Phosphate group variants include, but are not limited to, saturated alkyl phosphonates, unsaturated alkenyl phosphonates, phosphorothioates, and phosphoramidites.

[0046] As used herein, the phrase "operably linked" refers to a functional linkage between two or more molecules, lipids, polypeptides, entities, moieties, etc.

[0047] As used herein, in the context of a polypeptide, the term "portion" refers to a segment derived from a polypeptide or one or more fragments of a polypeptide.

[0048] As used herein, the term "payload" refers to any molecule that is associated with the lipoprotein system for delivery to a cell, tissue, subject, or biological system.

[0049] The "percent (%) sequence identity" with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in the candidate sequence that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps (if necessary) to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full-length of the sequences being compared.

[0050] As used herein, the term "protective mutation" is a mutation in a polypeptide or polynucleotide relative to a parent polypeptide or parent polynucleotide, the presence of which prevents, protects, or shields the polynucleotide or polypeptide, or a cell, organ, system, or organism containing the polypeptide or polynucleotide, from one or more cellular consequences or conditions associated with a disease or disorder (e.g., neurodegeneration). As non-limiting examples, a protective mutation can prevent or reduce the occurrence of aggregation of a polypeptide containing the protective mutation, reduce binding to heparin, inflammation, tauopathy disease progression, and / or neurodegeneration.

[0051] As used herein, the term "region" refers to a partition or general area. In some embodiments, when referring to a protein or polypeptide, a region may include a linear sequence of amino acids along the protein, or may include a three-dimensional region, an epitope, and / or an epitope cluster. In some embodiments, a region includes a terminal region. As used herein, the term "terminal region" refers to a region located at the end or terminus of a given agent. When referring to a protein, a terminal region may include the N-terminus and / or the C-terminus. The N-terminus refers to the end of the protein that contains amino acids with free amino groups. The C-terminus refers to the end of the protein that contains amino acids with free carboxyl groups. Thus, the N-terminal region and / or the C-terminal region may include the N-terminus and / or the C-terminus and surrounding amino acids. In some embodiments, the N-terminal region may include amino acids of any length including the N-terminus but not including the C-terminus. In some embodiments, the C-terminal region may include amino acids of any length including the C-terminus but not including the N-terminus.

[0052] As used herein, "structured sequence region" refers to a region of a polypeptide that contains one or more folding patterns formed by a stable arrangement of the amino acid residues of the polypeptide in its main chain. The folding pattern may be an alpha helix, a beta conformation, or a beta turn.

[0053] As used herein, the phrase "signal sequence" refers to a sequence that directs the transport or localization of a polypeptide.

[0054] As used herein, the term "treating" refers to partially or completely alleviating, ameliorating, improving, relieving one or more symptoms or features of a particular infection, disease, condition and / or disorder, delaying its onset, inhibiting its progression, lessening its severity and / or reducing its incidence. For example, "treating" cancer may refer to inhibiting the survival, growth and / or spread of a tumor. Treatment can be administered to subjects who do not show signs of the disease, condition and / or disorder and / or to subjects who only show early signs of the disease, condition and / or disorder to reduce the risk of developing pathology associated with the disease, condition and / or disorder.

[0055] As used herein, a "variant" is a form or version of a polypeptide or polynucleotide that differs in some respect from other forms of the same polypeptide or polynucleotide or from a polypeptide or polynucleotide reference standard. Such a polypeptide or polynucleotide reference standard can be a parent polypeptide or polynucleotide, or a starting polypeptide or polynucleotide having differences in structure, sequence, or function that distinguish the variant from the starting or reference standard.

[0056] As used herein, the term "unique polypeptide" is intended to describe a polypeptide having a distinguishing feature or combination of distinguishing features that is not present in another polypeptide. Distinguishing features can refer to amino acid sequence (natural and / or non-natural), secondary structure, post-translational modification, chemical modification, and / or functional characteristics in the polypeptide.

[0057] As used herein, the term "unique lipid" is intended to describe a lipid that has a distinguishing feature or a combination of distinguishing features not found in lipids. The distinguishing feature can refer to the primary structure of the lipid, the conformation of the lipid, the functional groups of the lipid, modifications of the lipid structure, and / or the charge of the lipid.

[0058] The details of one or more embodiments of the present disclosure are set forth in the following accompanying description. Although any materials and methods similar to or equivalent to those described herein can be used in the practice or testing of the present disclosure, preferred materials and methods are now described. Other features, objects and advantages of the present disclosure will be apparent from the specification. In the specification, unless the context clearly provides otherwise, the singular also includes the plural. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present disclosure belongs. In the event of a conflict, this specification shall prevail. DETAILED DESCRIPTION

[0059] The present disclosure provides a lipoprotein system comprising apolipoprotein and lipids (e.g., glycerophospholipids). Apolipoprotein is well-known for its ability to bind lipid molecules and cross the blood-brain barrier. The system disclosed herein utilizes this feature of apolipoprotein to design particles (e.g., nanoparticles), which are optionally bound to a payload, can regulate lipid metabolism and deliver the payload directly to the brain. Particles disclosed herein can be formulated into various shapes, e.g., discs. The lipoprotein system disclosed herein can be used to treat diseases or conditions (e.g., diseases of the nervous system, autoimmune diseases, cardiovascular diseases, vascular diseases, respiratory diseases, metabolic diseases, gastrointestinal diseases, genetic syndromes, cancer or multi-system diseases, etc.).

[0060] The present disclosure exploits the unprecedented discovery of the biophysical advantages of lipoprotein systems comprising apolipoproteins, such as apolipoprotein E (APOE), and glycerophospholipids, such as phosphatidylglycerol (PG). The incorporation of glycerophospholipids, such as PG lipids, imparts to the lipoprotein systems of the present disclosure improved polydispersity, thermal stability, and binding affinity compared to other lipoprotein systems. The present disclosure also provides novel peptide sequences for use in such lipoprotein systems. Novel polypeptide sequences are generated by assembling the sequences disclosed herein feature by feature to produce functional polypeptide sequences that can be formulated into lipoprotein systems. The present disclosure provides lipoprotein systems of varying sizes, shapes, dimensions, lipid compositions, and / or apolipoprotein content that exhibit beneficial biophysical properties.

[0061] The arrangement and / or positioning of components within the system can be optimized to achieve a particular form or function. In some embodiments, the lipids can be arranged as a bilayer, and the polypeptides of the present disclosure can surround or coat the lipids. In some embodiments, one or more lipids can exist as a core and be surrounded by a lipid monolayer operably associated with the polypeptides of the present disclosure. In some embodiments, the lipoprotein system can be organized into concentric spherical layers.

[0062] 47, 48, 49, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or more polypeptides. 47, 48, 49, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or more lipids. In some embodiments, the lipoprotein system can comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or more payloads.

[0063] The lipoprotein systems of the present disclosure can be formatted into a specific form. In some embodiments, the identity of the lipids in the lipoprotein system can be varied to adjust the shape or form of the system. In some embodiments, the lipoprotein system can have a disc-like, spherical, cylindrical, lamellar, oblate, or elliptical form. In a preferred embodiment, the lipoprotein system has a disc-like shape.

[0064] The amount and ratio of lipoprotein system components can be changed with any amount according to desired payload, form, function, structure or any combination thereof. In some embodiments, the amount of each component can be expressed as the relative ratio (molar ratio) of each component based on the number of molecules. In some embodiments, the lipoprotein system can include polypeptides and lipids in a specific molar ratio. When there is more than one lipid or polypeptide in the system, the ratio reflects the ratio of the combined polypeptide to the lipid, or the ratio of the polypeptide to the combined lipid, or the ratio of the combined polypeptide to the combined lipid, as the case may be.Non-limiting examples of polypeptide to lipid molar ratios include 1:30, 1:60, 1:90, 1:120, 1:150, 1:180, 1:210, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:40, 1:50, 1:70, 1:80, 1:100, 1:110, 1:130, 1:140, 1:160, 1:170, 1:190, 1:200, 1:220, 1:230, 1:240, 1:250, 1:300, 1:400, 1:500, 1:600, 1:700, 1:800, 1:900, 1:1000, 1:5000, 1:10000, 2:1, 2:3, 2:5, 2:7, 2:9, 3:1, 3:2, 3:4, 3:5, 3:7, 3:8, 3:10, 3:20, 3:40, 3:50, 3:70, 3:80, 3:100, 3:110, 3:130, 3:140, 3:160, 3:170, 3:190, 3:200, 3:220, 3:230, 3:250, 3:400, 3:500, 3:700, 3:800, 3:1000, 3:5000, 3:10000, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 5:2, 7:2, 9:2, 1:3, 2:3, 4:3, 5:3, 7:3, 8:3, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 10:3, 20:3, 40:3, 50:3, 70:3, 80:3, 100:1, 110:1, 120:1, 130:1, 140:1, 150:1, 160:1, 170:1, 180:1, 190:1, 200 :1, 210:1, 220:1, 230:1, 240:1, 250:1, 300:1, 400:1, 500:1, 600:1, 700:1, 800:1, 900:1, 100:3, 110:3, 130:3, 140:3, 160:3, 170:3, 190:3, 200:3, 220:3, 230:3, 250:3, 400:3, 500:3, 700:3, 800:3, 1000:1, 5000:1, 1000:3, 5000:3, 10000:1 and / or 10000:3 mol / mol.

[0065] In some embodiments, the ratio of polypeptide to lipid can be designed to reflect the ratio of apolipoprotein to lipid found in naturally occurring high-density lipoprotein particles (HDL). In some embodiments, the lipoprotein system of the present disclosure may include one or more lipid bilayers. In some embodiments, the lipoprotein system of the present disclosure may be a unilamellar or multilamellar vesicle. The unilamellar vesicle may be a small unilamellar vesicle (SUV) with a diameter of about 20 to about 100 nm, a large unilamellar vesicle (LUV) with a diameter of about 100 to about 1000 nm, or a giant unilamellar vesicle (GUV) with a diameter of >1000 nm. In some embodiments, the diameter of the multilamellar vesicle (MLV) may be >500 nm, wherein the concentric bilayers form a multilamellar structure.

[0066] peptides

[0067] A polypeptide is a polymer of amino acid residues linked together, most commonly by peptide bonds. As used herein, the term encompasses proteins, polypeptides, or peptides of any size, structure, or function. A polypeptide may comprise natural amino acids, non-natural amino acids, or combinations thereof. A polypeptide may comprise a gene product, a naturally occurring polypeptide, a synthetic polypeptide, a homolog, an ortholog, an analog, or other equivalents thereof.

[0068] Polypeptides can be single molecules or can be multimolecular complexes, such as dimers, trimers or tetramers. They can also include single-chain or multi-chain polypeptides and can be associated or linked. The term polypeptide can also apply to amino acid polymers in which one or more amino acid residues are artificial chemical analogs of the corresponding naturally occurring amino acids. When the polypeptide is a multimolecular complex, it can include at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000 or more molecules. These molecules may be derived from the same parent protein or different parent proteins.

[0069] The polypeptides of the present disclosure can be a parent protein or can be derived from a parent protein. Any naturally occurring protein can be a parent protein of the polypeptides of the present disclosure. In some embodiments, polypeptide variants can be derived from a parent protein or can be variants of a parent protein. The parent protein can be a mammalian protein. In some embodiments, the parent protein can be from a mammal, such as, but not limited to, humans, mice, rats, dogs, pigs, goats, llamas, or sheep.

[0070] In some embodiments, a polypeptide of the present disclosure may be an apolipoprotein or may be derived from an apolipoprotein.

[0071] In some embodiments, the polypeptide sequences of the present disclosure can be adjusted to optimize one or more characteristics, including but not limited to polypeptide expression in vitro or in vivo, cholesterol efflux, thermal stability, half-life in biological fluids (e.g., cerebrospinal fluid, plasma), payload delivery, and / or blood-brain barrier penetration. In some embodiments, the polypeptide sequences of the present disclosure can be adjusted to increase polypeptide expression in vitro or in vivo, increase cholesterol efflux, increase thermal stability, increase half-life in biological fluids (e.g., cerebrospinal fluid, plasma), enhance payload delivery, and / or improve blood-brain barrier penetration. In some embodiments, the polypeptide sequences of the present disclosure can be adjusted to reduce expression in vitro or in vivo, reduce cholesterol efflux, reduce thermal stability, reduce half-life in biological fluids (e.g., cerebrospinal fluid, plasma), delay payload delivery, and / or reduce blood-brain barrier penetration.

[0072] Polypeptides of the present disclosure may comprise one or more amino acids that can simulate activation sequences. For example, glutamic acid can be used as a mimic of phosphothreonine and / or phosphoserine. Alternatively, mimics may result in inactivation or produce an inactivated product containing the mimics, for example, phenylalanine can serve as an inactivated substitute for tyrosine, or alanine can serve as an inactivated substitute for serine.

[0073] The polypeptide of the present disclosure may include one or more post-translational modifications (PTMs). After the lipoprotein system is applied to a subject, or after the polynucleotide encoding the polypeptide of the present disclosure is applied to a subject, modification may occur in vitro, in vivo, and / or within the cell. Post-translational modifications (PTMs) of the present disclosure include, but are not limited to, oxidation, carbamylation, oxidation-carbamylation, acetylation, phosphorylation, ubiquitination, biotinylation, carboxylation, deamidation, deamination, deacetylation, dihydroxylation, dephosphorylation, formylation, γ-carboxyglutamate, glutathionylation, saccharification, hydroxylation, methylation, nitration, sumoylation, N-transglutamination or O-transglutamination, glycosylation, and farnesylation. In some embodiments, glycosylation may be N-glycosylation or O-glycosylation. In some embodiments, glycosylation may be O-glycosylation. As a non-limiting example, O-glycosylation may be sialylation. The polypeptide may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more PTMs. In some embodiments, the PTMs may be present in one or more regions of the polypeptide, including the structural sequence region, the N-terminal sequence region, the C-terminal sequence region, or a combination thereof.

[0074] Polypeptides can be reversibly or irreversibly chemically cross-linked or cyclized through natural bonds (e.g., disulfide bonding, natural chemical linkages) or non-natural bonds (e.g., bonds produced by "click chemistry", olefin metathesis, or bifunctional probe dimerization). In some embodiments, the polypeptides of the present disclosure can be cross-linked, which involves chemically linking two or more molecules through covalent bonds. Cross-linking can be performed within a region or portion of a polypeptide, or between two or more polypeptides. The connection between two groups on a single polypeptide produces intramolecular cross-linking, which stabilizes the tertiary or quaternary structure of the polypeptide. The connection between groups on two different polypeptides produces intermolecular cross-linking, which stabilizes polypeptide-polypeptide interactions. Cross-linking can be achieved by using homobifunctional cross-linking reagents, heterobifunctional cross-linking reagents, or photoreactive cross-linking reagents. Non-limiting examples of homobifunctional cross-linkers include disuccinimidyl suberate (DSS), disuccinimidyl tartrate (DST), dithiobisuccinimidyl propionate (DSP), bismaleimidoethane (BMOE), 1,4-bismaleimidobutane (BMB), 1,8-bismaleimidodiethylene glycol (BMB-PEG2), 1,3-dichloroacetone or DTME. Non-limiting examples of heterobifunctional cross-linkers include m-maleimidobenzoyl-N-hydroxysuccinimide ester (MDS), N-γ-maleimidobutyryloxysuccinimide ester (GMBS), N-(ε-maleimidocaproyloxy)succinimide ester (EMCS), or N-(ε-maleimidocaproyloxy)sulfosuccinimide ester (sulfo-EMCS). In some embodiments, more than one type of cross-link can be used within a given polypeptide molecule. In some embodiments, cross-linking is accomplished by oxidation, reduction, UV radiation, esterification, hydrolysis, intercalating agents, anti-tumor agents, formaldehyde, formalin, silica compounds, siloxane bridges, or photocrosslinking. In some embodiments, linkers such as small organic molecules (esters, amines) or inorganic molecules (silica, siloxanes), including microparticles or nanoparticles thereof, can be used to cross-link multiple molecules.

[0075] The polypeptides of the present disclosure are in some cases composed of multiple polypeptide chains that are linked together by covalent bonds or non-covalent forces to form dimers, trimers, tetramers, pentamers, hexamers, heptamers, oligomers (<50 polypeptide chains), or multimers (>50 polypeptide chains). Each of these proteins may have multiple N-termini and C-termini. Alternatively, the termini of the polypeptides may be modified so that they begin or end (as the case may be) with a non-polypeptide-based moiety (such as an organic conjugate).

[0076] In some embodiments, the lipoprotein systems or polypeptides of the present disclosure can be modified to reduce their immunogenicity. Immunogenicity is the result of a series of reactions to substances that are considered foreign and may include the production of neutralizing and non-neutralizing antibodies, the formation of immune complexes, complement activation, mast cell activation, inflammation, hypersensitivity reactions, and allergic reactions. There are many factors that can contribute to protein immunogenicity, including but not limited to protein sequence, route and frequency of administration, and patient population. Protein engineering can be used to reduce the immunogenicity of the compositions of the present disclosure. Modifications that reduce immunogenicity can include modifications that reduce the binding of processed peptides derived from the sequences of the compositions of the present disclosure to MHC proteins. For example, amino acids can be modified so that there is little or no immunogenic epitope in the compositions of the present disclosure that is predicted to bind to any common MHC allele. Several methods are known in the art to identify MHC binding epitopes of known protein sequences, and these methods can be used to score epitopes in the compositions of the present disclosure. Such methods are disclosed in US Patent Publication Nos. US20020119492, US20040230380, and US20060148009; the contents of each of which are incorporated by reference in their entirety.

[0077] Epitope identification and subsequent sequence modification can be used to reduce immunogenicity. Identification of immunogenic epitopes can be achieved by physical means or computational means. Physical methods for epitope identification can include, for example, mass spectrometry and tissue culture / cell technology. Computational methods that utilize information, structure and / or proteomics data related to antigen processing, loading and display to identify peptides that may be produced by antigen processing and may have good binding characteristics in the MHC groove can also be adopted. One or more mutations can be introduced into the polypeptide of the present disclosure so that the identified epitope has lower immunogenicity or is non-immunogenic while maintaining functionality.

[0078] In some embodiments, protein modifications such as glycosylation and PEGylation that are introduced into the structure of the compositions of the present disclosure to interfere with antigen processing and peptide loading may also be used in the present disclosure. Compositions of the present disclosure may also include non-classical amino acid side chains. Any method for reducing immunogenicity discussed in International Patent Publication WO2005051975 may be used in the present disclosure (the contents of the patent publication are incorporated by reference in their entirety).

[0079] In some embodiments, the polypeptides of the present disclosure may include modified amino acids or amino acid derivatives. As used herein, the term "modified amino acid" or "amino acid derivative" refers to a non-proteinogenic amino acid, i.e., an amino acid that is not one of the 20 common amino acids. In some embodiments, the modified amino acid or amino acid derivative is formed by post-translational modification. In some embodiments, the modified amino acid or amino acid derivative is formed by artificial synthesis. In some embodiments, the modified amino acid or amino acid derivative includes a side chain substituent substituted by another substituent. In some embodiments, the modified amino acid or amino acid derivative includes a protecting group or other substituent bound to a functional group such as an amino or carboxyl group. Exemplary modifications include, but are not limited to, carboxylation, hydroxylation, acylation, alkylation, amidation, acetylation, lipidation, lipoylation, hypusine formation, prenylation, glipyatyon, phosphopantetheinylation, retinylidene schiffer base, and the like. Schiffbase formation, diphtheria amide formation, amide bond formation, butyrylation, γ-carboxylation, glycosylation, polysialylation, iodination, nucleotide addition, phosphate or phosphoramidate formation, phosphorylation, adenylation, uridylation, propionylation, pyroglutamate formation, S-glutathionylation, S-nitrosylation, S-sulfinylation, S-sulfinylation, S-sulfonylation, succinylation, glycation, carbamylation, carbonylation, biotinylation, oxidation, pegylation, ISGylation, SUMOylation, ubiquitination, neddylation, pupylation, citrullination, deimination, deamidation, eliminylation, and disulfide bridges.

[0080] Apolipoproteins and apolipoprotein variants

[0081] In some embodiments, the polypeptides of the present disclosure may include or may be derived from a parent polypeptide such as an apolipoprotein. As used herein, "apolipoprotein" may be used to refer to a protein that binds to a lipid and / or is capable of interacting with a lipid. The binding or interaction of an apolipoprotein with a lipid may be direct or indirect.

[0082] Apolipoprotein can be preproform (also referred to as preprotein form herein), mature form or processed form. For example, when apolipoprotein is initially expressed in the endoplasmic reticulum as preproprotein or preproform. The preprotein form can include a signal sequence, which can be removed after transport through the Golgi apparatus and arriving at its target location (for example, extracellular space). This form can be referred to as "mature form" in this article. Subsequently, a part for the amino acid sequence can be cut under the action of an intracellular or extracellular proteolytic enzyme, produces the processed form of apolipoprotein.

[0083] The apolipoprotein of the present disclosure can be apolipoprotein E (APOE), apolipoprotein A (APOA), apolipoprotein B (APOB), apolipoprotein C (APOC), apolipoprotein D (APOD), apolipoprotein F (APOF), apolipoprotein H (APOH), apolipoprotein J (APOJ), apolipoprotein L (APOL), apolipoprotein M (APOM) or apolipoprotein O (APOO) or any known apolipoprotein. In a preferred embodiment, the apolipoprotein is apolipoprotein E.

[0084] In some embodiments, the apolipoprotein can be a human apolipoprotein. In some embodiments, the apolipoprotein can be a non-human apolipoprotein. Non-limiting examples of non-human species include monkeys, chimpanzees, rats, mice, horses, sheep, cats, dogs, cows, or rabbits.

[0085] Apolipoprotein variants

[0086] In some embodiments, an apolipoprotein may differ in some respects from other forms of apolipoprotein (i.e., be a variant of another apolipoprotein). Such an apolipoprotein may be a parent apolipoprotein or a starting apolipoprotein polypeptide or polynucleotide having differences in structure, sequence, or function that distinguish the apolipoprotein variant from a starting or reference standard.

[0087] The apolipoprotein variants of the present disclosure can be apolipoprotein E (APOE), apolipoprotein A (APOA), apolipoprotein B (APOB), apolipoprotein C (APOC), apolipoprotein D (APOD), apolipoprotein F (APOF), apolipoprotein H (APOH), apolipoprotein J (APOJ), apolipoprotein L (APOL), apolipoprotein M (APOM) or apolipoprotein O (APOO) or any known apolipoprotein variant.

[0088] In general, apolipoprotein variants can have at least about 70%, at least 80% or at least 90% identity with other forms of protein. As used herein, percent identity is defined as the number of residues (amino acid or nucleic acid) identical with the second amino acid or nucleic acid sequence in every 100 residues of the first sequence after comparing sequences and introducing room to realize maximum percent identity if necessary. The final value of percent identity may be subject to the impact of the room and penalty introduced in the calculation to reach the maximum. The percent identity of apolipoprotein can be calculated for the entire apolipoprotein, or only calculated for a region or part thereof. In some embodiments, the percent identity can be at least 70%, 75%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9%. In some embodiments, the percent identity can be at least 60%-70%, 65%-75%, 70%-80%, 75%-85%, 85%-95%, 90-99%, or 95-99.99%. The percent identity of the polypeptide to a known apolipoprotein may be 10% to 20%, 10% to 25%, 10% to 50%, 10% to 60%, 10% to 70%, 10% to 80%, 10% to 90%, 10% to 95%, 20% to 25%, 20% to 50%, 20% to 60%, 20% to 70%, 20% to 80%, 20% to 90%, 20% to 95%, 20% to % identity to a particular reference polynucleotide or polypeptide can be determined by sequence alignment programs such as the BLAST suite (Stephen F. Altschul et al. (1997), "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs," Nucleic Acids Res. 25:3389-3402).In the context of two or more nucleic acid or polypeptide sequences, the term "identical" or "identity" percentage refers to that two or more sequences or subsequences are identical or have a specified percentage of identical amino acid residues or nucleotides (i.e., 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, 99.5%, 99.8%, 99.9% or 100% identity within a specific region, e.g., an entire polypeptide sequence of the present disclosure or a single domain of a polypeptide of the present disclosure) when compared and aligned for maximum correspondence over a comparison window or specified region, as measured using a sequence comparison algorithm or by manual alignment and visual inspection. Such sequences that are at least about 80% identical are referred to as "substantially identical." In some embodiments, two sequences are 100% identical. In some embodiments, two sequences are 100% identical over the entire length of one of the sequences (eg, the shorter of the two sequences when the sequences are of different lengths). In various embodiments, identity can refer to complementarity of the test sequences.

[0089] In some embodiments, the identity exists over a region that is at least about 2 to about 400 amino acids or nucleotides in length. In some embodiments, the identity exists over a region that is at least about 2 to about 390, at least about 2 to about 380, at least about 2 to about 370, at least about 2 to about 360, at least about 2 to about 350, at least about 2 to about 340, at least about 2 to about 330, at least about 2 to about 320, at least about 2 to about 310, at least about 2 to about 300, at least about 2 to about 290, at least about 2 to about 280, at least about 2 to about 270, at least about 2 to about 260, at least about 2 to about 250, at least about 2 to about 200, at least about 2 to about 150, at least about 2 to about 100 amino acids or nucleotides in length. In some embodiments, the identity exists over a region that is at least about 2 to about 90, at least about 2 to about 85, at least about 2 to about 80, at least about 2 to about 75, at least about 2 to about 70, at least about 2 to about 65, at least about 2 to about 60, at least about 2 to about 55, at least about 2 to about 50, at least about 2 to about 45, at least about 2 to about 40, at least about 2 to about 35, at least about 2 to about 30, at least about 2 to about 25, at least about 2 to about 20, at least about 2 to about 10, or at least about 2 to about 5 amino acids or nucleotides in length. In some embodiments, the identity exists over a length of at least about 3 to about 400, about 4 to about 400, about 5 to about 400, about 6 to about 400, about 7 to about 400, about 8 to about 400, about 9 to about 400, about 10 to about 400, about 11 to about 400, about 12 to about 400, about 13 to about 400, about 14 to about 400, about 15 to about 400, about 16 to about 400, about 17 to about 400, about 18 to about 400, about 19 to about 400, or about 20 to about 25. or about 400, about 20 to about 400, about 21 to about 400, about 22 to about 400, about 23 to about 400, about 24 to about 400, about 25 to about 400, about 26 to about 400, about 27 to about 400, about 28 to about 400, about 29 to about 400, about 30 to about 400, about 31 to about 400, about 32 to about 400, about 33 to about 400, about 34 to about 400, or about 35 to about 400 amino acids or nucleotides.In some embodiments, the identity exists over a length of at least about 40 to about 400, about 45 to about 400, about 50 to about 400, about 55 to about 400, about 60 to about 400, about 61 to about 400, about 62 to about 400, about 63 to about 400, about 64 to about 400, about 65 to about 400, about 66 to about 400, about 67 to about 400, about 68 to about 400, about 69 to about 400, about 70, about 400, about 71 to about 400, about 72 to about 400, about 73 to about 400, about 74 to about 400, about 75 to about 400, about 80 to about 400, about 85 to about 400, about 90 to about 400, about 100 to about 400, about 150 to about 400, about 200 to about 400, about 250 to about 400, about 300 to about 400, about 350 to about 400 amino acids or nucleotides. In some embodiments, the identity exists over a length of at least about 2 to about 343, about 3 to about 343, about 4 to about 343, about 7 to about 343, about 9 to about 343, about 11 to about 343, about 15 to about 343, about 16 to about 343, about 20 to about 343, about 25 to about 343, about 62 to about 343, about 2 to about 317, about 3 to about 317, about 4 to about 317, about 7 to about 317, about 9 to about 317, about 11 to about 317, about 15 to about 317, about 16 to about 317, about 20 to about 317, about 25 to about In some embodiments, the present invention relates to a region of about 317, about 62 to about 317, about 2 to about 300, about 3 to about 300, about 4 to about 300, about 7 to about 300, about 9 to about 300, about 11 to about 300, about 15 to about 300, about 16 to about 300, about 20 to about 300, about 25 to about 300, about 62 to about 300, about 2 to about 62, about 3 to about 62, about 4 to about 62, about 7 to about 62, about 9 to about 62, about 11 to about 62, about 15 to about 62, about 16 to about 62, about 20 to about 62, or about 25 to about 62 amino acids or nucleotides.

[0090] In some embodiments, apolipoprotein variant can be a substitution variant of another apolipoprotein. When referring to polypeptides, "substitution variants" refer to polypeptides that remove at least one amino acid residue in a natural or starting sequence and insert different amino acids in the same position in situ. The substitution can be single, wherein only one amino acid is substituted in the molecule, or the substitution can be multiple, wherein two or more amino acids are substituted in the same molecule. In some embodiments, apolipoprotein can include conservative amino acid substitutions. As used herein, the term "conservative amino acid substitution" refers to replacing the amino acids typically present in a sequence with different amino acids of similar size, charge or polarity. Examples of conservative substitutions include replacing another non-polar residue with a non-polar (hydrophobic) residue (such as isoleucine, valine and leucine). Similarly, examples of conservative substitutions include replacing another polar residue with a polar (hydrophilic) residue, such as the substitution between arginine and lysine, the substitution between glutamine and asparagine, and the substitution between glycine and serine. In some embodiments, the apolipoprotein variants may include non-conservative replacements. Examples of non-conservative replacements include replacements of polar (hydrophilic) residues (such as cysteine, glutamine, glutamic acid or lysine) with non-polar (hydrophobic) amino acid residues (such as isoleucine, valine, leucine, alanine, methionine), and / or replacements of non-polar residues with polar residues.

[0091] In some embodiments, the apolipoprotein variant can be an insertion variant. As used herein, when referring to polypeptides, the term "insertion variant" is one in which one or more amino acids are inserted immediately adjacent to an amino acid at a specific position in a native or starting sequence. As used herein, the term "immediately adjacent" refers to the adjacent amino acids that are attached to the α-carboxyl or α-amino functional group of the starting or reference amino acid.

[0092] In some embodiments, apolipoprotein variants can be deletion variants. As used herein, when referring to polypeptides, the term "deletion variant" is one in which one or more amino acids in the native or starting amino acid sequence are removed. Generally, a deletion variant will lack one or more amino acids in a specific region of the polypeptide.

[0093] The system of the present disclosure can also comprise peptides that mimic the structure and / or activity of apolipoprotein.As non-limiting examples, the present disclosure can include any one of the agonists described in US 6,004,925, US 6,037,323, US 6,046,166, US 5,840,688; the contents of each of the patents are incorporated herein by reference in their entirety.

[0094] In some embodiments, the apolipoprotein may be derived from a non-human apolipoprotein or may be a variant of a non-human apolipoprotein. The non-human species may be a monkey, chimpanzee, rat, mouse, horse, sheep, cat, dog, cow and / or rabbit.

[0095] Apolipoprotein or apolipoprotein variants disclosed herein can have N-terminal or C-terminal truncations relative to other forms of apolipoprotein polypeptides, or can have one or more internal deletions or insertions. The apolipoprotein used in the method and composition of the present disclosure can be a polymer of apolipoprotein or its part, for example, two or more copies of the apolipoprotein or its variant or part connected by a joint. The apolipoprotein used in the method and composition of the present disclosure can be a chimeric apolipoprotein comprising the sequence of two different apolipoproteins (or its variants). In addition, apolipoprotein can be incorporated into a peptide or another protein sequence, for example, as a part for a fusion protein. For example, a peptide sequence can be a purification and / or detection tag.

[0096] Non-limiting examples of apolipoproteins are provided in Table 1.

[0097] Table 1. Apolipoproteins

[0098]

[0099]

[0100] In some embodiments, the apolipoprotein is a variant or mutation of a protein in Table 1.

[0101] APOE

[0102] The polypeptide disclosed herein may be apolipoprotein E (APOE), or a derivative and / or variant of APOE. This protein family binds lipids and interacts with low-density lipoprotein receptors (LDLRs), which are important for the processing of triglyceride-rich proteins. In peripheral tissues, APOE is produced by the liver and macrophages and mediates cholesterol metabolism. In the central nervous system, APOE is produced by astrocytes and transports cholesterol to neurons via APO receptors (members of the LDLR family).

[0103] APOE is widely distributed in various lipoproteins: it is present in chylomicron remnants, mature very low density lipoprotein (VLDL), VLDL remnants, low density lipoprotein (LDL) and high density lipoprotein (HDL). It binds with high affinity to the LDL receptor and the LRP receptor family. APOE helps to clear chylomicrons and VLDL remnants. About 60% of plasma APOE is present in HDL, which exchanges APOE with other lipoproteins. APOE is synthesized by hepatocytes, macrophages and brain astrocytes. APOE and APOA work together to control the efflux of cholesterol from cells. It also has antioxidant properties and plays a role in regulating inflammatory responses. Different variants of APOE may have different affinities for lipids, lipoproteins and receptors, and the selection of APOE variants included in the lipoprotein system of the present disclosure can be adjusted accordingly.

[0104] Apolipoproteins of the present disclosure can be modifications (e.g., mutations) of other apolipoproteins (e.g., APOE, APOE1, APOE2, APOE3, APOE4, or APOE5). Apolipoprotein mutations can include amino acid substitutions, deletions, insertions, and amino acid sequence changes (e.g., reverse sequences, scrambled sequences, multidomain sequences, switch domain sequences).

[0105] In some embodiments, the APOE variant can be APOE3 (ENSP00000252486; SEQ ID NO: 1), APOE2 (C130, C176) (SEQ ID NO: 2), APOE4 (R130, R176) (SEQ ID NO: 3). This precursor form of the protein contains a signal sequence.

[0106] In some embodiments, the apolipoprotein can be a region of another apolipoprotein, such as amino acids (aa) 18-317 of APOE3 (SEQ ID NO: 268); aa 18-317 of APOE2 (SEQ ID NO: 267); aa 18-317 of APOE4 (SEQ ID NO: 269).

[0107] In some embodiments, the polypeptide of the present disclosure may be an APOE variant associated with a disease or condition. In some embodiments, the polypeptide of the present disclosure may be an APOE variant associated with a disease, such as, but not limited to, a neurological disorder (e.g., Alzheimer's disease), cardiovascular disease (e.g., hyperlipoproteinemia, familial abnormal betalipoproteinemia, hypercholesterolemia, familial mixed hyperlipidemia), or kidney disease (e.g., lipoprotein glomerulopathy). APOE variants have been identified as the main genetic modifiers of Alzheimer's disease (AD), causing susceptibility to late-onset AD. APOE affects the production, aggregation, and clearance of amyloid proteins, is a component of amyloid plaques, and exacerbates tau-mediated neurodegeneration. APOE2 has some protective effects against Alzheimer's disease, while APOE4 is associated with an increased risk of Alzheimer's disease (Corder et al., Nat Genet. 1994; 7: 180–4; Corder et al., Science. 1993; 261: 921–3; Poirier et al., Lancet. 1993; 342: 697–9; the contents of each of which are incorporated herein by reference in their entirety). APOE also regulates lipid metabolism and cardiovascular risk. Approximately 5%-10% of APOE2 homozygous individuals exhibit type III hyperlipoproteinemia (HLP III), while other APOE variants are associated with autosomal dominant HLP III. HLP III is characterized by elevated plasma cholesterol and triglyceride levels, as well as the presence of nodular or striated palmar xanthomas. In some embodiments, the polypeptides disclosed herein may be APOE variants associated with cognitive decline in aging. Individuals carrying the APOE-ε4 allele develop memory decline before age 60 and show a greater degree of exacerbation than non-carriers (Caselli et al., N Engl J Med. 2009; 361: 255–63).

[0108] In some embodiments, the APOE variant can be the APOE Christchurch variant (also referred to herein as APOECh or APOE3ChC). As used herein, the term APOE Christchurch variant can be used to refer to an APOE protein sequence that contains serine at position 154 of the APOE protein sequence (SEQ ID NO: 1-3). As used herein, APOE Christchurch can also be referred to as APOE(R136S) or the APOE of SEQ ID NO: 268, 267, 269, which contains amino acids (aa) 18-317 of SEQ ID NO: 1-3. In some embodiments, the APOE Christchurch variant can be the APOE3 Christchurch variant (also referred to herein as APOE3Ch, APOE3-Ch, APOE3ChC or APOE3(R154S) (SEQ ID NO: 330). In some embodiments, the APOE Christchurch variant can be the APOE2 Christchurch variant (also referred to herein as APOE2Ch, APOE2-Ch, APOE2ChC or APOE2(R154S). The ability of the APOE Christchurch variant to suppress tau pathology has been demonstrated by in vitro experiments, which showed that the APOE Christchurch variant may behave like APOE2; both bind poorly to heparin (APOE3ChC < APOE2) (Mahley et al., 1999 Lipid Res. 40, 1933–1949 (1999); Arboleda-Velsquez et al. 2019, Nat Med 25, 1680–1683, the contents of which are incorporated herein by reference in their entirety). These findings suggest that after amyloid formation, the pathogenic event chain associated with AD may be broken by APOE3ChC, and regardless of the mechanism, the Christchurch mutation has a protective effect.

[0109] In some embodiments, APOE variant can be APOE Jacksonville variant (also referred to herein as APOEJac).As used herein, term APOE Jacksonville variant can be used to refer to the APOE protein sequence comprising glutamic acid (V254E) at position 254 of APOE protein sequence (SEQ ID NO:1-3).As used herein, APOEJacksonville can also be referred to as APOE (V236E) relative to SEQ ID NO:268, 267 or 269 APOE, which comprises amino acid (aa) 18-317 of SEQ ID NO:1-3.In some embodiments, APOE Jacksonville variant can be APOE3Jacksonville variant (also referred to herein as APOE3Jac or APOE3 (V254E)) (SEQ ID NO:331). In some embodiments, the APOE Jacksonville variant can be the APOE2 Jacksonville variant (also referred to herein as APOE2Jac or APOE3(V254E). Liu et al. have found that the APOE Jacksonville variant is associated with healthy brain aging and a reduced risk of AD and dementia with Lewy bodies (DLB) (Liu CC et al. Sci Transl Med. 2021 Sep 29;13(613):eabc9375; the contents of which are incorporated herein by reference in their entirety).

[0110] The APOE variants disclosed herein may comprise one or more mutations relative to APOE3 (SEQ ID NO: 1), APOE2 (SEQ ID NO: 2), APOE4 (SEQ ID NO: 3) at the positions discussed herein.

[0111] In some embodiments, the APOE protein can be a mutant of human APOE3 (SEQ ID NO: 1; Reference Ensemble PRT ID ENSP00000252486). Relative to APOE3, mutants include A6T (SEQ ID NO: 388), A7V (SEQ ID NO: 389), L9P (SEQ ID NO: 390), V10I (SEQ ID NO: 391), T11A (SEQ ID NO: 392), T11S (SEQ ID NO: 393), F12Y (SEQ ID NO: 394), F12L (SEQ ID NO: 395), L13R (SEQ ID NO: 396), A18P (SEQ ID NO: 397), A18T (SEQ ID NO: 398), E21K (SEQ ID NO: 399), A23V (SEQ ID NO: 400), V24L (SEQ ID NO: 401), T26_E29dup (SEQ ID NO: 402), P28L (SEQ ID NO: 403), E31K (SEQ ID NO: 404), R33C (SEQ ID NO: 405), NO:405), R33H (SEQ ID NO:406), Q35R (SEQ ID NO:407), E37K (SEQ ID NO:408), Q39R (SEQ ID NO:409), G41S (SEQ ID NO:410), R43del (SEQ ID NO:411), R43C (SEQ ID NO:412), R43H (SEQ ID NO:413), L46P (SEQ ID NO:415), L48V (SEQ ID NO:416), R50C (SEQ ID NO:417), R50S (SEQ ID NO:418), R50G (SEQ ID NO:419), R50P (SEQ ID NO:420), R50H (SEQ ID NO:421), R50L (SEQ ID NO:422), R56H (SEQ ID NO:423), T60A (SEQ ID NO:424), Q64H (SEQ ID NO:425), E68del (SEQ ID NO:426), E68V (SEQ ID NO:428), E68D (SEQ ID NO:429), L69Q (SEQ ID NO:430), L69P (SEQ ID NO:431), L70F (SEQ ID NO:432), Q73R (SEQ ID NO:433), V74A (SEQ IDNO:434)、Q76R(SEQ ID NO:435)、E77K(SEQ ID NO:436)、A80E(SEQ ID NO:437)、M82R(SEQ ID NO:438)、D83E(SEQ ID NO:439)、E84K(SEQ ID NO:440)、M86V(SEQ ID NO:441)、E88Q(SEQ ID NO:442)、L89S(SEQ IDNO:443)、K90E(SEQ ID NO:444)、K90N(SEQ ID NO:445)、Y92C(SEQ ID NO:446)、K93fs(SEQID NO:447)、K93T(SEQ ID NO:448)、K93R(SEQ ID NO:449)、K93N(SEQ ID NO:450)、S94*(SEQ ID NO:451)、Q99K(SEQ ID NO:452)、Q99R(SEQ ID NO:453)、P102R(SEQ ID NO:454)、V103L(SEQ ID NO:455)、V103L(SEQ ID NO:456)、A104T(SEQ ID NO:457)、E106Q(SEQ IDNO:458)、R108_A118dup(SEQ ID NO:459)、R108Q(SEQ ID NO:460)、R110fs(SEQ ID NO:461)、R110Q(SEQ ID NO:461)、S112Y(SEQ ID NO:462)、K113E(SEQ ID NO:463)、E114K(SEQID NO:464)、L115R(SEQ ID NO:465)、A117V(SEQ ID NO:466)、Q119P(SEQ ID NO:467)、A120S(SEQ ID NO:468)、A120D(SEQ ID NO:469)、R121W(SEQ ID NO:470)、G123R(SEQ IDNO:471)、D128N(SEQ ID NO:472)、V129M(SEQ ID NO:473)、G131C(SEQ ID NO:474)、R132C(SEQ ID NO:475)、R132L(SEQ ID NO:476)、Q135R(SEQ ID NO:477)、Y136C(SEQ ID NO:478)、R137C(SEQ ID NO:479)、R137G(SEQ ID NO:480)、R137H(SEQ IDNO:481)、G138C(SEQID NO:482)、V140L(SEQ ID NO:483)、V140M(SEQ ID NO:484)、L144I(SEQ ID NO:485)、G145R(SEQ ID NO:486)、G145S(SEQ ID NO:487)、G145D(SEQ ID NO:488)、G145A(SEQ IDNO:489)、Q146*(SEQ ID NO:490)、L151M(SEQ ID NO:491)、R152W(SEQ ID NO:492)、R152Q(SEQ ID NO:493)、V153M(SEQ ID NO:494)、R154S(SEQ ID NO:330)、R154fs(SEQ ID NO:495)、R154C(SEQ ID NO:496)、R154L(SEQ ID NO:497)、S157F(SEQ ID NO:498)、L159P(SEQID NO:499)、R160G(SEQ ID NO:500)、163C(SEQ ID NO:501)、R163H(SEQ ID NO:502)、K164Q(SEQ ID NO:503)、L167del(SEQ ID NO:504)、R168H(SEQ ID NO:505)、D169Y(SEQ IDNO:506)、D172N(SEQ ID NO:507)、Q174K(SEQ ID NO:508)、V179A(SEQ ID NO:509)、Y180H(SEQ ID NO:510)、Q181E(SEQ ID NO:511)、Q181H(SEQ ID NO:512)、A184S(SEQ ID NO:513)、G187A(SEQ ID NO:514)、G187V(SEQ ID NO:515)、G191_R198dup(SEQ ID NO:516)、E189K(SEQ ID NO:517)、R190C(SEQ ID NO:518)、G191S(SEQ ID NO:519)、S193R(SEQ IDNO:520)、R196C(SEQ ID NO:521)、R198C(SEQ ID NO:522)、G200R(SEQ ID NO:523)、R207S(SEQ ID NO:524)、R207C(SEQ ID NO:525)、R207H(SEQ ID NO:526)、R207P(SEQ IDNO:527)、V208L(SEQ ID NO:528)、V208M(SEQ ID NO:529)、V213G(SEQ ID NO:530)、G214S(SEQID NO:531)、G218R(SEQ ID NO:532)、G218S(SEQ ID NO:533)、Q219E(SEQ ID NO:534)、P220L(SEQ ID NO:535)、L221P(SEQ ID NO:536)、Q222*(SEQ ID NO:537)、Q222K(SEQ IDNO:538)、Q222R(SEQ ID NO:539)、R224P(SEQ ID NO:540)、R224L(SEQ ID NO:541)、A225T(SEQ ID NO:542)、A227S(SEQ ID NO:543)、W228*(SEQ ID NO:544)、G229R(SEQ ID NO:545)、G229V(SEQ ID NO:546)、E230K(SEQ ID NO:547)、R231Q(SEQ ID NO:548)、A234T(SEQID NO:549)、A234V(SEQ ID NO:550)、R235W(SEQ ID NO:551)、R235Q(SEQ ID NO:552)、E238del(SEQ ID NO:553)、E238D(SEQ ID NO:554)、M239I(SEQ ID NO:555)、G240R(SEQ IDNO:556)、S241R(SEQ ID NO:557)、T243fs(SEQ ID NO:558)、R242W(SEQ ID NO:559)、R242G(SEQ ID NO:560)、R242P(SEQ ID NO:561)、T243N(SEQ ID NO:562)、R246S(SEQ ID NO:563)、R246C(SEQ ID NO:564)、R246P(SEQ ID NO:565)、D248E(SEQ ID NO:566)、E249K(SEQID NO:567)、E249Q(SEQ ID NO:568)、E256V(SEQ ID NO:569)、R258H(SEQ ID NO:570)、A259P(SEQ ID NO:571)、E262K(SEQ ID NO:572)、E263K(SEQ ID NO:573)、Q267R(SEQID NO: 574), V254E (SEQ ID NO: 331), R269fs (SEQ ID NO: 575), R269C (SEQ ID NO: 576), R269G (SEQ ID NO: 577), E273G (SEQ ID NO: 578), A274G (SEQ ID NO: 579), Q276* (SEQ ID NO: 580), A277V (SEQ ID NO: 581), R278C (SEQ ID NO: 582), L279fs (SEQ ID NO: 583), W282C (SEQ ID NO: 584), E284G (SEQ ID NO: 585), E284D (SEQ ID NO: 586), L286M (SEQ ID NO: 587), V287M (SEQ ID NO: 588), D289A (SEQ ID NO: 589), R292C (SEQ ID NO: 590), R292H (SEQ ID NO: 591), W294C (SEQ ID NO: 592), A295T (SEQ ID NO: 593), G296R (SEQ ID NO: 594), G296W (SEQ ID NO: 595), L297P (SEQ ID NO: 596), E299Q (SEQ ID NO: 597), K300R (SEQ ID NO: 598), K300N (SEQ ID NO: 599), V301L (SEQ ID NO: 600), A303S (SEQ ID NO: 601), V305M (SEQ ID NO: 602), T307I (SEQ ID NO: 603), A309T (SEQ ID NO: 604), P311A (SEQ ID NO: 605), S314R (SEQ ID NO: 606), *318ext (SEQ ID NO: 607), W38* (SEQ ID NO: 608), E98fs (SEQ ID NO: 609), A117T (SEQ ID NO: 610), L122M (SEQ ID NO: 611), Q141R (SEQ ID NO: 612), R160C (SEQ ID NO: 613), R163P (SEQ ID NO: 614), K164E (SEQ ID NO: 615), R165P (SEQ ID NO: 616), A170P (SEQ ID NO: 617) and G183A (SEQ ID NO: 618). In some embodiments, relative to APOE3 (SEQ IDNO.: 1-3), the APOE protein can include more than one mutation, for example, more than two mutations, more than three mutations, more than four mutations, more than five mutations, etc.

[0112] In some embodiments, the APOE protein can be a mutant of SEQ ID NO: 5. Exemplary mutations include S2I (SEQ ID NO: 619), G4E (SEQ ID NO: 620), A5T (SEQ ID NO: 621), S6F (SEQ ID NO: 622), R7K (SEQ ID NO: 623), P12S (SEQ ID NO: 624), N14K (SEQ ID NO: 625), P17S (SEQ ID NO: 626), P18L (SEQ ID NO: 627), D19N (SEQ ID NO: 628), W20C (SEQ ID NO: 629), I22fs (SEQ ID NO: 630), T23K (SEQ ID NO: 631), G24D (SEQ ID NO: 632), G24V (SEQ ID NO: 633), and K26fs (SEQ ID NO: 634) (see SEQ ID NOs: 619-634).

[0113] APOA

[0114] In some embodiments, the polypeptides of the present disclosure may include or may be derived from APOA. In some embodiments, APOA may be APOA1 (also referred to herein as apolipoprotein AI, Apo AI, ApoA-I, Apo A1, ApoA1), APOA2 (also referred to herein as apolipoprotein A-II, Apo A-II, ApoA-II, Apo A2, ApoA2), APOA4 (also referred to herein as apolipoprotein A-IV, Apo A-IV, ApoA-IV, Apo A4, ApoA4), and / or APOA5 (also referred to herein as apolipoprotein AV, ApoA-V, ApoA-V, Apo A5, ApoA5).

[0115] In some embodiments, the polypeptides disclosed herein comprise or are derived from APOA1 or a variant thereof. APOA1 is a 243-amino acid protein. The APOA1 gene is located on chromosome 11 and is part of the APOA1 / C3 / A4 / A5 gene cluster. It is synthesized in the liver and intestine. The concentration of APOA1 is controlled by its degradation rate. APOA1 constitutes 70% of HDL apolipoproteins. It activates LCAT and is also an anti-inflammatory molecule and antioxidant. Plasma levels of APOA1 vary depending on the measurement method and population.

[0116] In some embodiments, the polypeptides disclosed herein comprise or are derived from APOA2 or a variant thereof. APOA2 is a 77-amino acid homodimer with a molecular weight of 17,400 Da. It is primarily expressed in the liver. APOA2 comprises approximately 20% of HDL protein. HDL particles contain only APOA1 or both APOA1 and APOA2. The concentration of APOA2 is determined by its production rate. It inhibits LPL activity (and may also inhibit HTGL) and serves as a cofactor for LCAT and CETP.

[0117] In some embodiments, the polypeptides disclosed herein comprise or are derived from APOA4 or a variant thereof. APOA4 is a glycoprotein with a molecular weight of 46,000 Da. It is synthesized in the intestine and incorporated into nascent chylomicrons. It is also present in HDL. Due to its relatively hydrophilic nature, it may be displaced from lipoproteins by APOE and circulates primarily as a lipid-free protein. It is involved in intestinal lipid absorption, participates in chylomicron assembly, and influences various aspects of lipoprotein response to diet.

[0118] In some embodiments, the polypeptides disclosed herein comprise or are derived from APOA5 or a variant thereof. APOA5 regulates the synthesis and secretion of VLDL in the liver. The gene encoding APOA5 is closely associated with triglyceride (TG) concentrations. APOA5 deficiency leads to type V dyslipidemia and reduced LPL activity after heparinization. On the other hand, its overexpression leads to reduced TG concentrations. APOA5 is synthesized in the liver.

[0119] In some embodiments, the APOA variant can include mutations R175C (referred to herein as APOA Paris or APOA1 Paris) and / or R197C (referred to herein as APOA Milano or APOA1 Milano) relative to ENSP00000236850 (SEQ ID NO: 9).

[0120] The APOA variants of the present disclosure may comprise one or more mutations at the positions discussed herein relative to REF ENSMBL PRT ID ENSP00000236850. Mutations relative to AOPAl include: Q267P (SEQ ID NO: 635), Q267E (SEQ ID NO: 636), Q267* (SEQ ID NO: 637), N265dup (SEQ ID NO: 638), T261S (SEQ ID NO: 639), A256T (SEQ ID NO: 640), L254R (SEQ ID NO: 641), Q240fs (SEQ ID NO: 642), F253L (SEQ ID NO: 643), V251D (SEQ ID NO: 644), L243V (SEQ ID NO: 645), L242M (SEQ ID NO: 646), L238del (SEQ ID NO: 647), L238P (SEQ ID NO: 648), E236K (SEQ ID NO: 649), P233L (SEQ ID NO: 650), K230del (SEQ ID NO: 651), NO:651), E229D (SEQ ID NO:652), E229K (SEQ ID NO:653), S228R (SEQ ID NO:654), S225G (SEQ ID NO:655), E222K (SEQ ID NO:656), E222* (SEQ ID NO:657), T221S (SEQ ID NO:658), A220P (SEQ ID NO:659), A218G (SEQ ID NO:660), E215Q (SEQ ID NO:661), L213V (SEQ ID NO:662), R212S (SEQ ID NO:663), R212I (SEQ ID NO:664), G209R (SEQ ID NO:665), N208Y (SEQ ID NO:666), E207D (SEQ ID NO:667), K206R (SEQ ID NO:668), L205V (SEQ ID NO:669), A204V (SEQ ID NO:670), R201H (SEQ ID NO:671), R201S (SEQ ID NO:672), A199T (SEQ ID NO:673), R197S (SEQ ID NO:674), Q196P (SEQID NO:675), E193K (SEQ ID NO:676), D192E (SEQ ID NO:677), D192N (SEQ IDNO:678)、Y190C(SEQ ID NO:679)、P189R(SEQ ID NO:680)、A188G(SEQ ID NO:681)、A188V(SEQ IDNO:682)、A188S(SEQ ID NO:683)、H186fs(SEQ ID NO:684)、R184L(SEQ ID NO:685)、A182V(SEQ ID NO:686)、A182E(SEQ ID NO:687)、A182T(SEQ ID NO:688)、R177L(SEQ ID NO:689)、A176V(SEQ ID NO:690)、A176S(SEQ ID NO:691)、A176T(SEQ ID NO:692)、E171V(SEQID NO:693)、E171K(SEQ ID NO:694)、E170K(SEQ ID NO:695)、E170*(SEQ ID NO:696)、L168P(SEQ ID NO:697)、L168V(SEQ ID NO:698)、S166R(SEQ ID NO:699)、L165R(SEQ IDNO:700)、K164N(SEQ ID NO:701)、E163G(SEQ ID NO:702)、E163K(SEQ ID NO:703)、Q162P(SEQ ID NO:704)、E160D(SEQ ID NO:705)、E160K(SEQ ID NO:706)、E160Q(SEQ ID NO:707)、H159Q(SEQ ID NO:708)、Q156R(SEQ ID NO:709)、R155L(SEQ ID NO:710)、A154V(SEQID NO:711)、A154T(SEQ ID NO:712)、E152K(SEQ ID NO:713)、Q151*(SEQ ID NO:714)、L150I(SEQ ID NO:715)、R147H(SEQ ID NO:716)、E144K(SEQ ID NO:717)、K142R(SEQ IDNO:718)、R140C(SEQ ID NO:719)、R140S(SEQ ID NO:720)、Y139*(SEQ ID NO:721)、Y139H(SEQ ID NO:722)、M136T(SEQ ID NO:723)、E134A(SEQ ID NO:724)、Q133E(SEQ ID NO:725)、W132C(SEQID NO:726)、W132L(SEQ ID NO:727)、K131del(SEQ ID NO:728)、K131M(SEQ ID NO:729)、K130R(SEQ ID NO:730)、Q129P(SEQ ID NO:731)、D127N(SEQ ID NO:732)、D126G(SEQ ID NO:733)、Y124*(SEQ ID NO:734)、P123S(SEQ ID NO:735)、P123T(SEQID NO:736)、V121A(SEQ ID NO:737)、A119V(SEQ ID NO:738)、D113E(SEQ ID NO:739)、M110I(SEQ ID NO:740)、R107S(SEQ ID NO:741)、E104D(SEQ ID NO:742)、E104K(SEQ IDNO:743)、K101E(SEQ ID NO:744)、E100G(SEQ ID NO:745)、L99P(SEQ ID NO:746)、D97N(SEQ ID NO:747)、F95Y(SEQ ID NO:748)、T92I(SEQ ID NO:749)、L88F(SEQ ID NO:750)、Q87H(SEQ ID NO:751)、K83N(SEQ ID NO:752)、F81Y(SEQ ID NO:753)、F81I(SEQ ID NO:754)、T78I(SEQ ID NO:755)、L71del(SEQ ID NO:756)、L71V(SEQ ID NO:757)、N67K(SEQID NO:758)、L66L(SEQ ID NO:759)、G63fs(SEQ ID NO:760)、L62F(SEQ ID NO:761)、A61T(SEQ ID NO:762)、S60P(SEQ ID NO:763)、S60A(SEQ ID NO:763)、G59V(SEQ ID NO:764)、G59A(SEQ ID NO:765)、Y53*(SEQ ID NO:766)、Y53C(SEQ ID NO:767)、G50V(SEQ ID NO:768)、G50S(SEQ ID NO:769)、S49N(SEQ ID NO:770)、S49I(SEQ ID NO:771)、S49R(SEQ IDNO:772)、D44E(SEQ ID NO:773)、V43L(SEQID NO: 774), V43M (SEQ ID NO: 775), V41L (SEQ ID NO: 776), T40A (SEQ ID NO: 777), A39V (SEQ ID NO: 778), R34L (SEQ ID NO: 779), R34Q (SEQ ID NO: 780), P31L (SEQ ID NO: 781), P31A (SEQ ID NO: 782), S30G (SEQ ID NO: 783), S30R (SEQ ID NO: 784), Q29H (SEQ ID NO: 785), Q29K (SEQ ID NO: 786), P28R (SEQ ID NO: 787), P28S (SEQ ID NO: 788), P27T (SEQ ID NO: 789), P27S (SEQ ID NO: 790), R19P (SEQ ID NO: 791), R19W (SEQ ID NO: 792), T14M (SEQ ID NO: 793) or V10M (SEQ ID NO: 794).

[0121] The APOA variants of the present disclosure may comprise one or more mutations at the positions discussed herein relative to REF ENSMBL PRT ID ENSP00000364478. Mutations relative to REF ENSMBL PRT ID ENSP00000364478 include: T226M (SEQ ID NO: 795), G209S (SEQ ID NO: 796), L202P (SEQ ID NO: 797), A199P (SEQ ID NO: 798), L198S (SEQ ID NO: 799), R197C (SEQ ID NO: 800), D181G (SEQ ID NO: 801), V180E (SEQ ID NO: 802), H179fs (SEQ ID NO: 803), R177P (SEQ ID NO: 804), R173P (SEQ ID NO: 805), P167R (SEQ ID NO: 806), E152G (SEQ ID NO: 807), K131* (SEQ ID NO: 808), L114P (SEQ ID NO: 809), NO: 809), Q108* (SEQ ID NO: 810), F95L (SEQ ID NO: 811), L84R (SEQ ID NO: 812), W74R (SEQ ID NO: 813), G50R (SEQ ID NO: 815), P27H (SEQ ID NO: 817), P27R (SEQ ID NO: 818), A21 8P (SEQ ID NO: 820), R2 12G (SEQ ID NO: 821), G45R (SEQ ID NO: 822), G45S (SEQ ID NO: 823), R40C (SEQ ID NO: 824), G35S (SEQ ID NO: 825), C34R (SEQ ID NO: 826), A28S (SEQ ID NO: 827), T27M (SEQ ID NO: 828), T27fs (SEQ ID NO: 829), A17_S23dup (SEQ ID NO: 830), F2 1del (SEQ ID NO: 831), S22P (SEQ ID NO: 832), F2 1L (SEQ ID NO: 833), F21S (SEQ ID NO: 834), F20L (SEQ ID NO: 835), H1 5L (SEQ ID NO: 837), P14S (SEQ ID NO: 838), G7S (SEQ ID NO: 839), R6Q (SEQ ID NO: 840), R6W (SEQ IDNO:841), G4R (SEQ ID NO:842), G3A (SEQ ID NO:843), G3R (SEQ ID NO:844) or M1I (SEQ ID NO:845).

[0122] Peptide characteristics

[0123] In some embodiments, the polypeptide of the present disclosure may include one or more components or features. As used herein, when referring to a protein or polypeptide, the term "feature" is defined as a unique component in a molecule based on an amino acid sequence. In some embodiments, the polypeptide of the present disclosure may include at least one structured sequence region. In some embodiments, the polypeptide of the present disclosure may include about 2 to about 30 structured sequence regions, for example, about 5 to about 25 structured sequence regions, about 10 to about 20 structured sequence regions, about 15 structured sequence regions, etc. In some embodiments, the polypeptide of the present disclosure may also include a signal sequence, an N-terminal sequence region, a C-terminal sequence region, or a hinge region, a joint region, or a combination thereof.

[0124] Features of the polypeptides of the present disclosure include surface expression, local conformational shape, fold, loop, half-loop, domain, half-domain, site, terminus, or any combination thereof.

[0125] In some embodiments, the polypeptides of the present disclosure comprise one or more surface manifestations. As used herein, when referring to a protein, the term "surface manifestation" refers to the polypeptide-based components of the protein that appear on the outermost surface.

[0126] In some embodiments, the polypeptides of the present disclosure comprise one or more local conformational shapes. As used herein, when referring to a protein, the term "local conformational shape" refers to a polypeptide-based representation of the protein's structure that is located within a definable space within the protein.

[0127] In some embodiments, the polypeptides of the present disclosure comprise one or more folds. As used herein, when referring to proteins, the term "fold" refers to the resulting conformation of an amino acid sequence after energy minimization. Folds may occur at the secondary or tertiary level of the folding process. Examples of secondary folds include beta sheets and alpha helices. Examples of tertiary folds include domains and regions formed due to high ability to aggregate or dissociate. Regions formed in this manner include hydrophobic pockets and hydrophilic pockets, among others.

[0128] In some embodiments, the polypeptides of the present disclosure comprise one or more turns. As used herein, when referring to protein conformation, the term "turn" refers to a bend that changes the direction of the peptide or polypeptide backbone and may involve one, two, three or more amino acid residues.

[0129] In some embodiments, the polypeptides of the present disclosure comprise one or more loops. As used herein, when referring to proteins, the term "loop" refers to a structural feature of a peptide or polypeptide that reverses the direction of the main chain of the peptide or polypeptide and includes four or more amino acid residues. Oliva et al. have identified at least five types of protein loops (Oliva, B. et al., An automated classification of the structure of protein loops. J Mol Biol. 1997. 266(4):814-30; the contents of which are incorporated herein by reference in their entirety).

[0130] In some embodiments, the polypeptide of the present disclosure comprises one or more half rings. As used herein, when referring to a protein, the term "half ring" refers to a portion of an identified ring whose number of amino acid residues is at least half of the number of the ring from which it originates. It should be understood that a ring may not always contain an even number of amino acid residues. Therefore, in the case where a ring contains or is identified as including an odd number of amino acids, the half ring of the odd number of rings will include the integer portion of the ring or the next integer portion (number of amino acids in the ring / 2+ / -0.5 amino acids). For example, a ring identified as a 7 amino acid ring can produce a half ring with 3 amino acids or 4 amino acids (7 / 2=3.5+ / -0.5, i.e., 3 or 4).

[0131] In some embodiments, the polypeptides of the present disclosure comprise one or more motifs and / or domains. A motif is a short sequence (<40 residues) pattern associated with one or more identifiable structural or functional characteristics or properties (e.g., binding ability, site for protein-protein interaction). In some embodiments, a motif refers to a unique structural site that performs a specific function. A domain is also a conserved sequence pattern that is defined as an independent functional and structural unit. A domain is typically longer than a motif. A domain consists of more than 40 residues and a maximum of 700 residues, with an average length of 100 residues. A domain may or may not contain a motif within its boundaries.

[0132] In some embodiments, the polypeptides of the present disclosure comprise one or more half-domains. As used herein, when referring to a protein, the term "half-domain" refers to a portion of an identified domain that has at least half the number of amino acid residues of the domain from which it is derived. It should be understood that a domain may not always contain an even number of amino acid residues. Thus, where a domain contains or is identified as comprising an odd number of amino acids, a half-domain of an odd-numbered domain will comprise an integer portion of the domain or the next integer portion (number of amino acids in the domain / 2 + / - 0.5 amino acids). For example, a domain identified as a 7-amino acid domain can produce a half-domain having 3 or 4 amino acids (7 / 2 = 3.5 + / - 0.5, i.e., 3 or 4). It should also be understood that subdomains can be identified within a domain or half-domain that possess fewer than all the structural or functional properties identified in the domain or half-domain from which they are derived. It should also be understood that the amino acids comprising any domain type herein do not necessarily have to be continuous along the backbone of the polypeptide (i.e., non-adjacent amino acids can structurally fold to produce a domain, half-domain, or subdomain).

[0133] In some embodiments, the polypeptides of the present disclosure comprise one or more sites. As used herein, the term "site" is used synonymously with "amino acid residue" and "amino acid side chain" when referring to amino acid-based embodiments. A site refers to a position within a peptide or polypeptide that can be modified, manipulated, altered, derivatized, or varied within the polypeptide-based molecules of the present disclosure.

[0134] Polypeptide features can be manipulated and / or modified by moving, exchanging, reversing, lacking, randomizing or duplicating. In addition, it should be understood that manipulation of features can produce the same results as the modification of the disclosed compositions. For example, manipulation involving a missing domain will result in changes in molecule length, just as modified nucleic acids can encode molecules less than full length. Modification and manipulation can be achieved by methods known in the art (such as site-directed mutagenesis). The activity of the resulting modified molecules can then be tested using in vitro or in vivo assays (such as assays described herein or any other suitable screening assays known in the art).

[0135] In some embodiments, the polypeptides of the present invention can be modified to adjust the binding of the polypeptide to lipids and / or receptors. Modifications can be introduced into polypeptides to change or adjust the interactions within or between polypeptides (e.g., Frieden et al., PNAS (109): 8913-8918, 2012; Fan D, et al. Biochemistry. 2004 May 4; 43(17): 5055-64, Zhang Y et al., Biochemistry. 2007 Sep 18; 46(37): 10722-32, and Georgiadou et al., PLoS One (6) e27037, 2011; the contents of each of which are incorporated herein by reference in their entirety). In some embodiments, the polypeptides of the present invention can be modified to change one or more properties, including but not limited to aggregation, complement fixation, half-life and / or stability.

[0136] In some embodiments, the polypeptide of the present disclosure may include one or more receptor binding domains. As used herein, a receptor binding domain may refer to a domain in a parent protein or polypeptide (e.g., apolipoprotein) that interacts with a receptor. The interaction of the domain with the receptor may cause the cell containing the receptor to perform a specific function and / or obtain a specific phenotype. In some embodiments, the polypeptide of the present disclosure may include a receptor binding domain of APOE or a receptor binding domain derived from APOE. In some embodiments, the receptor may be a low-density lipoprotein receptor (LDLR), an LDL receptor-related protein (LRP, such as LRP1, LRP4, LRP8), a very low-density lipoprotein receptor (VLDLR), a scavenger receptor class B member (SCARB1), an apolipoprotein B receptor (APOBR), a nuclear receptor subfamily 1 group H member 2 (NR1H2) and / or a nuclear receptor subfamily 2 group F member 2 (NR2F2). In some embodiments, the receptor binding domain may include a protein derived from APOE3 (SEQ ID NO: 1), APOE2 (SEQ ID NO: 2) or APOE4 (SEQ ID NO:3) or amino acid 120, 125, 130, 135, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 165, 170, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195 80 to amino acids 125, 130, 135, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 165, 170, 175, 180, 185. Non-limiting examples of receptor binding domains can include regions such as aa 130-150, 142-160, 148-168, 154-168, 160-178 of APOE3 (SEQ ID NO: 1), APOE2 (SEQ ID NO: 2), or APOE4 (SEQ ID NO: 3), or variants thereof. In some embodiments, the receptor binding domain may include RLASHLRKLRKRLLRDADDLQKRLA (SEQ ID NO: 851). In some embodiments, the receptor binding domain may include one or more mutations to modulate receptor binding properties. The polypeptides of the present disclosure may also include one or more mutations to modulate accessibility to the receptor binding sequence. In some embodiments, the compositions of the present disclosure may include point mutations in the binding region that increase receptor and substrate binding. In some embodiments, the compositions of the present disclosure may include point mutations in the binding region that reduce receptor and substrate binding.In some embodiments, the compositions of the present disclosure may comprise point mutations in the binding region that independently modulate receptor binding and substrate binding. For example, in some embodiments, the compositions of the present disclosure may comprise point mutations in the binding region that increase receptor binding and decrease substrate binding.

[0137] In some embodiments, the polypeptides of the present disclosure may include mutations that affect the aggregation propensity of the polypeptides. Mutations may include, for example, F275A (SEQ ID NO: 846), W282R (SEQ ID NO: 847), V287A (SEQ ID NO: 848), L297Q (SEQ ID NO: 849), and V305E (SEQ ID NO: 850) of APOE3 (SEQ ID NO: 1).

[0138] In some embodiments, the polypeptides of the present disclosure may include one or more heparin binding regions and / or heparan sulfate proteoglycan binding regions. The heparin binding region may be derived from a parent protein, such as, but not limited to, apolipoproteins, e.g., APOE. The heparin binding region in APOE may include residues near residues 142-147, 160-165, 243-272, 261-290 of SEQ ID NOs: 1-3 (Weisgraber et al., J Biol Chem. 1986; 261: 2068-2076; the contents of which are incorporated herein by reference in their entirety).

[0139] In some embodiments, the polypeptides of the present disclosure may comprise one or more glycosylation sites, which refer herein to sites in the polypeptides of the present disclosure that can be enzymatically modified to comprise a carbohydrate moiety. In some embodiments, the apolipoprotein variant may comprise one or more mutations that increase glycosylation of the polypeptide. Non-limiting examples include F275A of APOE3 (SEQ ID NO: 1), APOE2 (SEQ ID NO: 2), or APOE4 (SEQ ID NO: 3). In some embodiments, the apolipoprotein variant may comprise one or more mutations to reduce glycosylation of the polypeptide. For example, residue 212 of SEQ ID NO: 1 (SEQ ID NO: 855), residue 212 of SEQ ID NO: 2 (SEQ ID NO: 856), or residue 212 of SEQ ID NO: 3 (SEQ ID NO: 857) may be mutated to alanine to prevent glycosylation thereof.

[0140] In some embodiments, the polypeptides of the present disclosure further comprise an affinity tag. Non-limiting examples of affinity tags include HHHHHH (SEQ ID NO: 852), WSHPQFEK (SEQ ID NO: 853) and / or DYKDDDDK (SEQ ID NO: 854). As used herein, the term "affinity tag" refers to a peptide sequence attached to a protein so that the protein can be purified from its crude biological source using affinity techniques. Examples of affinity tags include, but are not limited to, chitin binding protein (CBP), maltose binding protein (MBP), FLAG tag, poly (His) tag, Strep-tag, and glutathione-S-transferase (GST). In some embodiments, the affinity tag can be removed by chemical agents or enzymatic means (such as proteolysis or intein splicing).

[0141] Structured sequence region

[0142] In some embodiments, the polypeptide of the present disclosure may include one or more structured sequence regions. As used herein, a "structured sequence region" refers to a region of a polypeptide containing one or more folding patterns formed by a stable arrangement of the amino acid residues of the polypeptide in its main chain. The folding pattern can be an alpha helix, a beta conformation, a beta turn, or a combination thereof. In some embodiments, the structured sequence region of a polypeptide may be derived from one or more parent proteins. Non-limiting examples of parent proteins include APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, or APOO. In some embodiments, a polypeptide includes a structured sequence region from a variety of parent proteins (e.g., a combination of parent proteins).

[0143] A structured sequence region (SSR) may be or include an alpha-helical sequence region. As used herein, an alpha-helical sequence refers to a type of structure in which the polypeptide backbone is tightly wound around an imaginary axis drawn longitudinally through the middle, with the R groups of the amino acids projecting outward from the backbone. In this conformation, each backbone NH group forms a hydrogen bond with the backbone C=O groups of the amino acids located in the first four residues of the protein sequence.

[0144] In some embodiments, the alpha helix sequence region can be or can include one or more amphipathic alpha helix sequence regions. Amphipathic (or amphipathic) helices are used to refer to alpha helices that can contain hydrophobic and hydrophilic amino acid residues, which are arranged in a manner such that two faces are formed on opposite sides of the helix, one face being hydrophobic and the other face being hydrophilic. In some embodiments, the amino acid sequence of the amphipathic helix can contain a hydrophilic amino acid at every second or third position in the sequence. The amphipathic alpha helices described herein can also contain an amino acid with a hydrophobic side chain at every third or fourth position.

[0145] In some embodiments, the SSR may comprise a helical bundle. As used herein, the term "helical bundle" refers to a protein fold composed of several alpha helices that may be or are nearly parallel or antiparallel to each other.

[0146] The SSR of the present disclosure may comprise one or more peptides. The SSR peptide may be of any length, for example, about 2-55 amino acids in length. In some embodiments, the peptide within the SSR may be 11 amino acids (herein "11-mer") or multiples thereof, such as, but not limited to, 22-mer, 33-mer, 44-mer, or 55-mer. In some embodiments, the SSR peptide may be an amphipathic alpha-helical sequence region or may be part of an amphipathic alpha-helical sequence region. In some embodiments, the polypeptide of the present disclosure may comprise about 5 to about 30 SSR peptides. The SSR peptides (SSRPs) may be derived from the same parent protein or the polypeptide of the present disclosure may comprise SSR peptides derived from 2 or more parent proteins. In some embodiments, one or more of the SSRPs may be repeated in the polypeptide of the present disclosure. In some embodiments, point mutations are introduced that affect aggregation propensity, glycosylation, receptor binding, or other properties. In some embodiments, a linker region between lipid-binding alpha helices may be introduced.

[0147] In some embodiments, the SSRP is not naturally occurring. In some embodiments, the SSRP may include a hydrophobic face that binds to lipids and a polar face with charged residues, thereby promoting its solubility in aqueous media and electrostatic interactions between lipoprotein systems. In some embodiments, positions 2, 3, 6, and 10 within the 11-mer may be hydrophobic residues, such as leucine. In some embodiments, positions 4, 5, 7, 8, and 9 may be polar or charged residues, such as glutamine or arginine. In some embodiments, position 1 or position 11 is a helix-breaking residue, such as Pro or Gly. In some embodiments, the SSRP is shorter or longer than 11 residues.

[0148] Table 2 provides non-limiting examples of SSRP sequences.

[0149] Table 2. Structured sequence region peptides

[0150]

[0151]

[0152] The polypeptides of the present disclosure may comprise a plurality of amphipathic alpha helices covalently linked together using the well-known and established fragment conjugation or ligation chemistry described by Dawson and Kent in their comprehensive review "Synthesis of Native Proteins by Chemical Ligation" 2000, Ann Rev Biochem 69:923-60 (the contents of which are incorporated herein by reference in their entirety). In some embodiments, the helices and linker segments may be linked as described in "Synthesis of Native Proteins by Chemical Ligation" 2000, Ann Rev Biochem 69:923-60. The alpha helices may be separated by short linker sequences that may be provided by natural or non-natural amino acid sequences. In some embodiments, the linker sequence may form an amino acid ring.

[0153] In some embodiments, the SSR may be or may include a β-conformation sequence region. As used herein, a "β-conformation sequence region" refers to a type of structure in which the polypeptide backbone extends in a zigzag pattern rather than a helical structure. In some embodiments, the zigzag polypeptide chains may be arranged side by side to form a β-sheet. The zigzag polypeptide chains may be arranged side by side to form a structure similar to a series of folds. Hydrogen bonds are formed between adjacent segments of the polypeptide chain. The individual segments that form the β-sheet are typically adjacent to each other on the polypeptide chain, but may also be far apart from each other in the linear sequence of the polypeptide; they may even be segments in different polypeptide chains. In some embodiments, adjacent polypeptide chains in a β-sheet may be parallel or antiparallel (having the same or opposite amino to carboxyl orientation, respectively). The β-sheet domain may be critical for establishing strong bonds with the lipids of the lipoprotein system of the present disclosure. In some embodiments, one or more amphipathic α-helical domains may be located between two β-sheet domains.

[0154] In some embodiments, the SSR may be or may include a beta turn region.As used herein, a "beta turn region" refers to a type of structure that connects the ends of two adjacent segments of a beta sheet.

[0155] In some embodiments, the structured sequence region of the present disclosure may include one or more folding patterns repeated once, twice, or more than three times, configured as, for example, ABABAB or AABBAABBAAABB or ABCABCABC or variants thereof. In these patterns, each letter A, B, or C represents a different folding pattern. In another embodiment, the polypeptide of the present disclosure may include two or more folding pattern component sequences, each component having one or more sequences. As a non-limiting example, the sequence may adopt a pattern repeated once, twice, or more than three times in each region, such as ABABAB or AABBAAABBAABB or ABCABCABC or variants thereof.

[0156] In some embodiments, an SSR can include one or more gap sequences adjacent to folding patterns present within the SSR. A gap sequence can connect adjacent folding patterns within the SSR.

[0157] In some embodiments, the polypeptides of the present disclosure may comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 SSRPs. In some embodiments, the structured sequence region peptide may comprise 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85 , 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, or 100 amino acids (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 97, 98, 99, or 100mer).

[0158] In some embodiments, the structured sequence region comprises hydrophobic residues on its inner surface. In some embodiments, the hydrophobic residues on the inner surface of the structured sequence region bind lipid acyl chains. In some embodiments, the structured sequence region comprises endogenous hydrophobic residues on its inner surface. In some embodiments, the structured sequence region comprises the substitution of any amino acid with a hydrophobic amino acid to have a hydrophobic residue on its inner surface. In some embodiments, the structured sequence region comprises the substitution of any amino acid with a hydrophobic amino acid to increase the hydrophobic residues on its inner surface. In some embodiments, the structured sequence region comprises the substitution of any hydrophilic amino acid or neutral amino acid with a hydrophobic amino acid to have a hydrophobic residue on its inner surface. In some embodiments, the structured sequence region comprises the substitution of any hydrophilic amino acid or neutral amino acid with a hydrophobic amino acid to increase the hydrophobic residues on its inner surface.

[0159] In some embodiments, the structuring sequence region comprises hydrophilic residues on its outer surface. In some embodiments, the hydrophilic residues on the outer surface of the structuring sequence region enable solubilization of the lipoprotein particle in an aqueous medium or solution.

[0160] In some embodiments, the structured sequence region comprises endogenous hydrophilic residues on its outer surface. In some embodiments, the structured sequence region comprises the substitution of any amino acid with a hydrophilic amino acid to have a hydrophilic residue on its outer surface. In some embodiments, the structured sequence region comprises the substitution of any amino acid with a hydrophilic amino acid to increase the hydrophilic residues on its outer surface. In some embodiments, the structured sequence region comprises the substitution of any hydrophobic amino acid or neutral amino acid with a hydrophilic amino acid to have a hydrophilic residue on its outer surface. In some embodiments, the structured sequence region comprises the substitution of any hydrophobic amino acid or neutral amino acid with a hydrophilic amino acid to increase the hydrophilic residues on its outer surface.

[0161] In some embodiments, the structured sequence region comprises high charge residues on its top or bottom surface. In some embodiments, the high charge residues are, for example, Arg or Glu. In some embodiments, the interaction between the top or bottom surfaces of adjacent peptides in the structured sequence region is an intramolecular interaction. In some embodiments, the interaction between the top or bottom surfaces of adjacent peptides in the structured sequence region is an intermolecular interaction.

[0162] In some embodiments, the structured sequence region comprises endogenous high-charge residues on its top or bottom surface. In some embodiments, the structured sequence region comprises endogenous (e.g., Arg or Glu) residues on its top or bottom surface. In some embodiments, the structured sequence region comprises the replacement of any amino acid with a high-charge amino acid to have a high-charge residue on its top or bottom surface. In some embodiments, the structured sequence region comprises the replacement of any amino acid with a high-charge amino acid to increase the high-charge residues on its top or bottom surface. In some embodiments, the structured sequence region comprises the replacement of any neutral amino acid with a high-charge amino acid to have a high-charge residue on its top or bottom surface. In some embodiments, the structured sequence region comprises the replacement of any neutral amino acid with a high-charge amino acid to increase the hydrophilic residues on its outer surface.

[0163] In some embodiments, the structured sequence region comprises substitutions of any amino acid with, for example, Arg or Glu, to have high charge residues on its top or bottom surface. In some embodiments, the structured sequence region comprises substitutions of any amino acid with, for example, Arg or Glu, to increase high charge residues on its top or bottom surface. In some embodiments, the structured sequence region comprises substitutions of any neutral amino acid with, for example, Arg or Glu, to have high charge residues on its top or bottom surface. In some embodiments, the structured sequence region comprises substitutions of any neutral amino acid with, for example, Arg or Glu, to increase hydrophilic residues on its outer surface.

[0164] In some embodiments, the residues on the top or bottom of the structured sequence region are replaced by natural or non-natural amino acids. In some embodiments, the residues on the top or bottom of the structured sequence region are replaced by natural or non-natural amino acids. In some embodiments, the residues on the top or bottom of the structured sequence region are replaced by Cys or Tyr. In some embodiments, the substituted residues on the top or bottom of the structured sequence region are cross-linked to multiple molecules by covalent or non-covalent bonds. In some embodiments, the covalent bond is a disulfide bond. In some embodiments, the structured sequence region provides a structural component for lipid binding. In some embodiments, the structured sequence region binds to ATP-binding cassette transporters (ABC transporters) and stimulates cholesterol efflux. In some embodiments, the structured sequence region is used as a site for chemical cross-linking. In some embodiments, the polypeptides of the present disclosure form dimers. In some embodiments, the polypeptides form homodimers. In some embodiments, the polypeptides form disulfide homodimers. In some embodiments, the polypeptides form dimers by utilizing protein dimerizing agents. As used herein, the term "protein dimerizer," also known as a chemical inducer of dimerization, refers to a compound that binds two different proteins and brings them into close proximity only in the presence of a dimerizer. Protein dimerizers are often used to build protein complexes. Exemplary protein dimerizing agents include, but are not limited to, FK1012 (a derivative of tacrolimus) for FKBP (FK506 binding protein) homodimers, FK506 (tacrolimus) for FKBP and calcineurin A (CNA) dimers, FKCsA for FKBP and CyP-Fas dimers, rapamycin for FKBP and FRB (FKBP-rapamycin binding) domain for mTOR dimers, coumarins for GyrB (DNA gyrase subunit B) homodimers, gibberellins for GAI (DELLA protein member) and GID1 (gibberellic acid insensitive dwarf 1) dimers, HaXS for SNAP tag and HaloTag dimers, TMP-HTag for eDHFR (dihydrofolate reductase) and HaloTag dimers, and ABT-737 for Bcl-xL and Fab (AZ1) dimers. In some embodiments, non-natural means include light-induced dimerization. Exemplary light-induced dimerization includes, but is not limited to, the use of light-sensitive proteins or photocaged chemical dimerization agents.

[0165] In some embodiments, the first or last residue in the SSRP is a helix-breaking residue, thereby allowing flexibility between sequential helices. In some embodiments, the helix-breaking residue is Pro or Gly. In some embodiments, SSRP stimulates ABCA (ATP-binding cassette transporter A) / ABCG (ATP-binding cassette transporter G)-mediated cholesterol efflux. In some embodiments, SSRP may be sufficient to stimulate ABCA / ABCG-mediated cholesterol efflux.

[0166] In some embodiments, SSRP may be derived from alignment of apolipoprotein consensus repeat units. In some embodiments, apolipoprotein consensus repeat units may be combined in a non-natural order. In some embodiments, apolipoprotein consensus repeat units may be derived from the sequence of non-human APOE. In some embodiments, apolipoprotein consensus repeat units may be derived from the sequence of other interchangeable apolipoproteins (e.g., ApoA1 or ApoA-1). In some embodiments, apolipoprotein consensus repeat units may be derived from the sequence of ApoA1 or ApoA-1.

[0167] In some embodiments, the structured sequence region may comprise point mutations or chemical cross-links to alter the accessibility and effective affinity of the binding region. In some embodiments, the structured sequence region may comprise point mutations that introduce additional Arg residues to alter the aggregation tendency and protease stability of the protein, as well as its half-life in the endosomal / lysosomal compartment. In some embodiments, the structured sequence region may comprise point mutations to alter the multimerization tendency of the polypeptide in solution.

[0168] N-terminal sequence region

[0169] In some embodiments, the polypeptide of the present disclosure may include an N-terminal sequence region. The N-terminal sequence region can be derived from any parent protein or polypeptide. In some aspects, the N-terminal sequence region is derived from apolipoprotein (referred to herein as "apolipoprotein N-terminal sequence region"). As non-limiting examples, apolipoprotein can be APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM or APOO. In some embodiments, the N-terminal sequence region can include a region or fragment of the terminal region of a parent protein or polypeptide. In some embodiments, the N-terminal sequence region can include a region or fragment of the N-terminal of a parent protein or polypeptide (terminating with an amino acid with a free amino group (NH2)). In some embodiments, the N-terminal region can include amino acids of any length including the N-terminal of a parent protein or polypeptide but not including the C-terminal. For example, the N-terminal sequence region may include 1-10, 5-15, 10-20, 15-25, 20-30, 25-35, 30-40, 35-45, 40-50, 45-55, 50-60, 55-65, 60-70, 65-75, 70-80, 75-85, 80-90, 85-95, 90-100, 95-105, 100-110, 105-115, 116-117, 117-118, 119-120, 220-221, 221-222, 222-223, 223-224, 225-225 5. 110-120, 115-125, 120-130, 125-135, 130-140, 135-145, 140-150, 145-155, 150-160, 155-165, 160-170, 165-175, 170-180, 175-185, 180-190, 185-195, 190-200, 195-205, 200-210, 205-215, 210-220, 215-225, 220-230, 225-235, 230-240, 235-245, 240-250, 245-255, 250-260, 255-265, 260-270, 265-275, 270-280, 275-285, 280-290, 285-295, 290-300, 295-305, 300-310, 305-315, 3 10-320, 315-325, 320-330, 325-335, 330-340, 335-345, 340-350, 345-355, 350-360, 355-365, 360-370, 365-375, 370-380, 375-385, 380-390, 385-395, 390-400, 400-500, 500-1000, 1000-5000.

[0170] In some embodiments, the N-terminal sequence region can be an APOEN terminal sequence region or an APOA1 N-terminal sequence region. Table 3 provides non-limiting examples of N-terminal sequence regions. The N-terminal sequence region can include more or fewer amino acids than any of the amino acids described in Table 3. Such amino acid sequences can include more or less about 1 amino acid, more or less about 2 amino acids, more or less about 3 amino acids, more or less about 4 amino acids, more or less about 5 amino acids, more or less about 6 amino acids, more or less about 7 amino acids, more or less about 8 amino acids, more or less about 9 amino acids, more or less about 10 amino acids, or more or less about greater than 10 amino acids.

[0171] Table 3. N-terminal sequence region

[0172]

[0173]

[0174] C-terminal sequence region

[0175] In some embodiments, polypeptide of the present disclosure may include a C-terminal sequence region. The C-terminal sequence region may be derived from any parent protein or polypeptide. In some aspects, the C-terminal sequence region is derived from apolipoprotein. As a non-limiting example, apolipoprotein may be APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM or APOO (herein "apolipoprotein C-terminal sequence region"). In some embodiments, the C-terminal sequence region may include a region or fragment of the terminal region of a parent protein or polypeptide. In some embodiments, the C-terminal sequence region may include a region or fragment of the C-terminal (terminating with an amino acid with a carboxyl group (NH2)) of a parent protein or polypeptide. In some embodiments, the C-terminal region may include an amino acid of any length including the C-terminal of a parent protein or polypeptide but not including N-terminal. For example, the C-terminal sequence region may include 1-10, 5-15, 10-20, 15-25, 20-30, 25-35, 30-40, 35-45, 40-50, 45-55, 50-60, 55-65, 60-70, 65-75, 70-80, 75-85, 80-90, 85-95, 90-100, 95-105, 100-110, 105-115, 116-117, 117-118, 119-120, 220-221, 221-222, 222-223, 224-225, 226-227, 227-228, 228-229, 229-300, 229-301, 229-302, 229-303, 229-304, 229-305 5. 110-120, 115-125, 120-130, 125-135, 130-140, 135-145, 140-150, 145-155, 150-160, 155-165, 160-170, 165-175, 170-180, 175-185, 180-190, 185-195, 190-200, 195-205, 200-210, 205-215, 210-220, 215-225, 220-230, 225-235, 230-240, 235-245, 240-250, 245-255, 250-260, 255-265, 260-270, 265-275, 270-280, 275-285, 280-290, 285-295, 290-300, 295-305, 300-310, 305-315, 3 10-320, 315-325, 320-330, 325-335, 330-340, 335-345, 340-350, 345-355, 350-360, 355-365, 360-370, 365-375, 370-380, 375-385, 380-390, 385-395, 390-400, 400-500, 500-1000, 1000-5000.

[0176] In some embodiments, the C-terminal sequence region can be an APOE C-terminal sequence region or an APOA1 C-terminal sequence region. Table 4 provides non-limiting examples of C-terminal sequence regions. The C-terminal sequence region can be any of the sequences in Table 4, or include more or fewer amino acids than the listed sequences. Such amino acid sequences can include more or less about 1 amino acid, more or less about 2 amino acids, more or less about 3 amino acids, more or less about 4 amino acids, more or less about 5 amino acids, more or less about 6 amino acids, more or less about 7 amino acids, more or less about 8 amino acids, more or less about 9 amino acids, more or less about 10 amino acids, or more or less about greater than 10 amino acids.

[0177] Table 4. C-terminal sequence region

[0178] CTERM ID Protein sequence SEQ ID NO: CTERM1 T SAAPVP SDNH 103 CTERM2 TQ - CTERM3 TNSIASTTVPLENQ 873

[0179] connector

[0180] In some embodiments, the lipoprotein system of the present disclosure may include a joint. As used herein, the term "joint" refers to any molecule or molecular group that connects two molecules or two parts of a molecule (such as two regions of a polypeptide). In some embodiments, the joint is a peptidyl joint. In some embodiments, the peptidyl joint includes a short peptide of 1 to about 25 amino acids. In some embodiments, the peptidyl joint includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 residues. In some embodiments, the peptidyl joint includes glycine and serine. In some embodiments, the residue of the peptidyl joint is glycine or serine. In some embodiments, the residue of the peptidyl joint is glycine and serine. In some embodiments, the peptidyl joint may be rich in glycine to contribute to flexibility, and rich in serine or threonine to contribute to solubility.

[0181] In some embodiments, the linker is a chemical linker. In some embodiments, the chemical linker is a covalent or non-covalent linker. In some embodiments, the chemical linker includes a chemically reactive functional group to react with a second chemically reactive functional group to form a covalent linker. In some embodiments, the chemical linker includes a resulting linker formed by reacting two reactive groups (parts) (for example, covalent reactive groups (for example, alkynes, thiols, azides, maleimides)). In some embodiments, the chemical linker is multivalent and / or formed by conjugated chemical techniques. The example of a chemical linker includes but is not limited to -O-, -S-, -C (O)-, -C (O) O-, -C (O) NH-, -S (O) 2NH-, -NH-, -NHC (O) NH-.

[0182] In some embodiments, the linker comprises a linear structure. In some embodiments, the linker comprises a nonlinear structure. In some embodiments, the linker comprises a branched structure. In some embodiments, the linker comprises a cyclic structure.

[0183] In some embodiments, a linker conjugates or connects multiple polypeptides or fragments of polypeptides or compounds. In some embodiments, a linker is combined with two polypeptides or compounds. In some embodiments, a linker is combined with three polypeptides or compounds.

[0184] In some embodiments, as used herein, "linker" (L) or "linker domain" or "linker region" or "linker module" or "peptide linker" refers to an oligopeptide or polypeptide region of about 1 to 100 amino acids in length that connects any domain / region of a polypeptide together (also referred to as a peptide linker). The peptide linker can be 1-40 amino acids in length, or 2-30 amino acids in length, or 20-80 amino acids in length, or 50-100 amino acids in length. The linker length can also be optimized based on the type of polypeptide or payload utilized and based on the crystal structure of the polypeptide or payload. In some cases, it may be preferable to select a shorter linker length. In some aspects, the peptide linker is composed of amino acids linked together by peptide bonds, preferably 1 to 20 amino acids linked by peptide bonds, wherein the amino acids are selected from the following 20 naturally occurring amino acids: glycine (G), alanine (A), valine (V), leucine (L), isoleucine (I), serine (S), cysteine ​​(C), threonine (T), methionine (M), proline (P), phenylalanine (F), tyrosine (Y), tryptophan (W), histidine (H), lysine (K), arginine (R), aspartic acid (D), glutamic acid (E), asparagine (N) and glutamine (Q). As will be appreciated by those skilled in the art, one or more of these amino acids may be glycosylated. In some aspects, the amino acids of the peptide linker may be selected from alanine (A), glycine (G), proline (P), asparagine (R), serine (S), glutamine (Q) and lysine (K).

[0185] In one example, an artificially designed peptide linker can preferably be composed of a polymer of flexible residues such as glycine (G) and serine (S) so that adjacent protein domains can move freely relative to each other. When it is necessary to ensure that two adjacent domains do not interfere with each other, longer linkers can be used. The selection of a specific linker sequence may involve whether it affects the biological activity, stability, folding, targeting and / or pharmacokinetic characteristics of the fusion construct.

[0186] The linker sequence can be a natural linker derived from a multidomain protein. A natural linker is a short peptide sequence that separates two different domains or motifs within a protein. For example, the linker sequence can be a hinge sequence derived from an apolipoprotein or a variant thereof. Table 5 provides non-limiting examples of linkers that can be used in the present disclosure.

[0187] Table 5. Connectors

[0188]

[0189]

[0190]

[0191]

[0192] hinge

[0193] In some embodiments, polypeptide of the present disclosure may include one or more hinge regions. As used herein, hinge is a molecule containing one or more amino acids, which connects two molecules or two parts of a molecule (such as two regions of a polypeptide), and promotes conformation or structural flexibility by allowing each of the two molecules or parts to move relative to each other. In some embodiments, hinge region can mediate the kinetics of lipid binding by providing the opening of the spiral required for starting lipid binding. In some embodiments, hinge region sequence mutations are to change the proteolytic stability of polypeptide of the present disclosure. Hinge can be located in structured sequence region, N-terminal sequence region, C-terminal sequence region, or between N-terminal sequence region and structured sequence region, or between structured sequence region and C-terminal sequence region, or between any other region or fragment of polypeptide of the present disclosure. Hinge region can be any suitable sequence derived from or obtained from any suitable molecule. Hinge sequence can be derived from all or part of apolipoprotein. In some embodiments, polypeptide of the present disclosure may not include hinge region. Table 6 provides non-limiting examples of hinge sequence.

[0194] Table 6. Hinge sequences

[0195]

[0196]

[0197]

[0198]

[0199]

[0200]

[0201] signal sequence

[0202] The polypeptides of the present disclosure may also comprise one or more additional features, such as one or more signal sequences.

[0203] Signal sequences (sometimes referred to as signal peptides, targeting signals, target peptides, localization sequences, transit peptides, leader sequences, or leader peptides) direct proteins or polypeptides to their designated cellular and / or extracellular locations. Protein signal sequences play a central role in the targeting and translocation of nearly all secreted proteins and many integral membrane proteins. In some embodiments, a signal sequence can direct the secretion of a polypeptide of the present disclosure.

[0204] A signal sequence is a short (5-30 amino acid long) peptide found at the N-terminus of most newly synthesized proteins that directs them to a specific location. Signal sequences are recognized by signal recognition particles (SRPs) and can be cleaved by type I and type II signal peptide peptidases. In some embodiments, the signal sequence can (but is not necessarily) be located at the N-terminus or C-terminus of a polypeptide and can (but is not necessarily) be cleaved from a polypeptide of the present disclosure.

[0205] In some embodiments, the signal peptide according to the present disclosure is located at the N-terminus of the target protein or the N-terminus of the proprotein form of the target protein. The signal peptide according to the present disclosure can be of eukaryotic origin, for example, a signal peptide of a eukaryotic protein, for example, of mammalian origin, for example, a signal peptide of a mammalian protein, more preferably of human origin, for example, a signal peptide of a mammalian protein.

[0206] In some embodiments, the signal sequence can be derived from apolipoprotein. Table 7 provides non-limiting examples of apolipoprotein signal sequences. All signal sequence parent apolipoproteins in Table 7 are derived from human apolipoprotein.

[0207] Table 7. Signal sequence

[0208]

[0209]

[0210] In addition to naturally occurring signal sequences (such as signal sequences from secreted proteins), signal sequences can also be modified variants of known protein signal sequences. For example, U.S. Patent Nos. 8,258,102 and 9,133,265 to Sleep disclose a modified albumin signal sequence having a secretion signal and an additional X1-X2-X3-X4-X5-motif that can increase protein secretion; U.S. Patent No. 9,279,007 to Do discloses a signal sequence of a modified fragment of human immunoglobulin heavy chain binding protein (Bip) that can enhance protein expression and secretion; U.S. Patent No. 8,148,494 to Leonhartsberger et al. discloses a signal peptide with a cleavage site that can be fused to a recombinant protein; the contents of each of these patents are incorporated herein by reference in their entirety.

[0211] The signal sequence can be selected based on its compatibility with the secretory pathway of the target cell type so that the payload is presented on the T cell surface. Other signal sequence variants that can be used in the polypeptides of the present invention may include those discussed in U.S. Patent Application Publication No. 2007 / 0141666, PCT Patent Application Publication No. 1993 / 018181; the contents of each of which are incorporated herein by reference in their entirety.

[0212] In other embodiments, the signal sequence may be a heterologous signal sequence from other organisms such as viruses, yeast, and bacteria, which can direct the polypeptide to a specific cellular site, such as the nucleus (eg, EP 1209450). Other examples can include an aspartic protease (NSP24) signal sequence from Trichoderma that can increase secretion of fusion proteins such as enzymes (e.g., U.S. Pat. No. 8,093,016 to Cervin and Kim); a bacterial lipoprotein signal sequence (e.g., PCT Application Publication No. 1991 / 09952 to Lau and Rioux), an E. coli enterotoxin II signal peptide (e.g., U.S. Pat. No. 6,605,697 to Kwon et al.), an E. coli secretion signal sequence (e.g., U.S. Pat. No. 2016 / 090404 to Malley et al.), a lipase signal sequence from methylotrophic yeast (e.g., U.S. Pat. No. 8,975,041), and a signal peptide for DNase from Corynebacterium (e.g., U.S. Pat. No. 4,965,197); the contents of each of which are incorporated herein by reference in their entirety.

[0213] Fusion peptide

[0214] In some embodiments, the polypeptides of the present disclosure may be fusion polypeptides. As used herein, the term "fusion polypeptide" may refer to a single, continuous peptide molecule containing two or more parent proteins, or regions or portions thereof, typically encoded by different genes. A fusion polypeptide may possess functional properties derived from each of the original proteins.

[0215] The components of a fusion polypeptide can be arranged from the amino terminus to the carboxyl terminus of a continuous region of the fusion protein. These regions can be directly connected to each other or connected by a linker. Protein linkers help fusion protein design by providing appropriate spacing between domains to support the correct folding of the fusion polypeptide. In some embodiments, the fusion polypeptide can include one or more parent proteins, such as, but not limited to, APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, APOO or variants thereof.

[0216] In some embodiments, a fusion polypeptide of the present disclosure may comprise a structural sequence region of a first apolipoprotein fused to a structural sequence region of a second apolipoprotein, wherein the first apolipoprotein may be APOE or APOA, and the second apolipoprotein may be APOE or APOA.

[0217] In some embodiments, the fusion polypeptides of the present disclosure may comprise a structural sequence region, an N-terminal sequence region, and a C-terminal sequence region, each sequence region independently derived from the same apolipoprotein or two or more apolipoproteins, such as, but not limited to, APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, APOO, or variants thereof.

[0218] In some embodiments, the fusion polypeptide may comprise one or more of a region, motif, surface expression, local conformational shape, fold, loop, half-loop, domain, half-domain, site, terminus, or any combination thereof from a parent protein, such as, but not limited to, APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, APOO, or a variant thereof.

[0219] Peptide sequence

[0220] In some embodiments, the apolipoprotein may comprise two or more polypeptide signature sequences disclosed herein. In some embodiments, the apolipoprotein sequence is a sequence disclosed in Table 8.

[0221] Table 8. Apolipoproteins

[0222]

[0223]

[0224]

[0225]

[0226]

[0227]

[0228]

[0229]

[0230]

[0231]

[0232]

[0233]

[0234]

[0235] lipids

[0236] Compositions of the present disclosure may include one or more lipids. As used herein, the term "lipid" refers to a biological molecule that is soluble in an organic solvent (e.g., chloroform) but has little solubility in water. In some embodiments, compositions of the present disclosure may include derivatives of lipids. As used herein, the term "derivative" refers to a molecule that is modified or changed in any way relative to a reference molecule or starting molecule (e.g., lipid).

[0237] In some embodiments, the lipid can be a fatty acid, a steroid or a sterol ester. In some embodiments, the fatty acid can be a free fatty acid, a wax, a triacylglycerol, a glycerophospholipid, a sphingolipid, a cardiolipin or a glycero-sphingolipid. In some embodiments, the lipid can be a cationic lipid, a fusogenic lipid, an anionic lipid, a neutral lipid or any combination thereof.

[0238] Organ selectivity of the compositions of the present disclosure can be achieved by adjusting the ratio of lipids, for example, to target the spleen or lung.

[0239] As used herein, the term "lipid" is intended to encompass all stereoisomers, geometric isomers, tautomers, and isotopes of the depicted or described structure associated with the lipid. When referring to a lipid feature or substituent, the term "optional" or "optionally" refers to a feature or substituent that may or may not be present. For example, "optionally substituted alkyl" encompasses "alkyl" and "substituted alkyl" as defined below. It will be understood by those skilled in the art that for any group containing one or more substituents, such group is not intended to introduce any sterically impractical, synthetically unfeasible, and / or inherently unstable substitution or substitution pattern. In some embodiments, isotopes of lipids can be used to facilitate the detection of lipids using mass spectrometry and / or to slow the oxidation rate of lipids (see Shchepinov, MS (2007). Rejuvenation research, 10(1), 47-60; the contents of which are incorporated herein by reference in their entirety).

[0240] The lipids described herein can have an asymmetric center, a geometric center (e.g., a double bond), or both. Unless a specific stereochemistry or isomeric form is specifically indicated, all chiral, diastereomer, racemic forms, and all geometric isomeric forms of the structure are contemplated. The lipids of the present disclosure containing asymmetrically substituted atoms can be separated in optically active or racemic forms. How to prepare optically active forms is well known in the art, such as by resolving racemic forms, by synthesizing from optically active starting materials, or by using chiral auxiliary agents. Geometric isomers of olefins, C=N double bonds, or other types of double bonds can be present in the lipids described herein, and all such stable isomers are included in the present disclosure. Specifically, cis and trans geometric isomers of the lipids of the present disclosure can also exist and can be separated as isomer mixtures or as separate isomeric forms.

[0241] The lipids described herein also encompass tautomeric forms. In some embodiments, tautomeric forms are produced by the exchange of a single bond with an adjacent double bond and the concomitant migration of a proton. Tautomeric forms include protonotropic tautomers of isomeric protonation states with the same empirical formula and total charge. Examples of protonotropic tautomers include keto-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, amide-imidic acid pairs, enamine-imine pairs, and cyclic forms in which protons can occupy two or more positions in a heterocyclic ring system, such as 1H-imidazole and 3H-imidazole, 1H-1,2,4-triazole, 2H-1,2,4-triazole and 4H-1,2,4-triazole, 1H-isoindole and 2H-isoindole, and 1H-pyrazole and 2H-pyrazole. Tautomeric forms can be in equilibrium or can be sterically locked into one form by appropriate substitution.

[0242] The lipids described herein also include all isotopes of atoms present in the intermediates or final compounds. "Isotopes" refers to atoms having the same atomic number but different mass numbers due to the different number of neutrons in the nucleus. Thus, for example, each individual hydrogen atom present in formula (200) can exist as a 1H, 2H (deuterium) or 3H (tritium) atom, preferably 1H or 2H. Similarly, for example, each individual carbon atom present in formula (200) can exist as 12 C. 13 C or 14 C atoms are present.

[0243] In some embodiments, the compositions of the present disclosure may include derivatives of any lipid described herein (referred to herein as "lipid derivatives"). As used herein, the term "derivative" refers to a form or version of a compound (e.g., a lipid) that differs from the parent compound (e.g., a lipid) by at least one atom or group.

[0244] In some embodiments, lipid derivatives may include hydrophilic groups. As used herein, the term "hydrophilic" and its grammatical equivalents refer to substances or structures having polar groups that readily interact with water. In some embodiments, lipids may include hydrophobic groups. As used herein, the term "hydrophobic" and its grammatical equivalents refer to substances or structures having polar groups that do not readily interact with water. For the structures provided herein, the following subscripts in brackets further define groups as follows: "(C n )” defines the exact number (n) of carbon atoms in the group. For example, “(C 2-10) alkyl" means an alkyl group having 2 to 10 carbon atoms (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10, or any range derivable therein (e.g., 3 to 10 carbon atoms). In some embodiments, a lipid derivative may differ from a parent lipid by comprising an alkyl group. "Alkyl" may refer to an aliphatic hydrocarbon group. The alkyl portion may be a "saturated alkyl" group, meaning that it does not contain any olefin or alkyne moieties. The alkyl portion may also be an "unsaturated alkyl" portion, meaning that it contains at least one olefin or alkyne moiety. In some embodiments, a lipid derivative may comprise an olefin moiety. An "olefin" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon double bond. In some embodiments, a lipid derivative may comprise an alkyne moiety. As used herein, " An "alkyne" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon triple bond. An alkyl moiety, whether saturated or unsaturated, may be branched, linear or cyclic. In addition, an alkyl moiety, whether saturated or unsaturated, may include branched, linear and / or cyclic moieties. Depending on the structure, an alkyl group may be a monoradical or a diradical (i.e., an alkylene group). In some embodiments, the lipid derivative may comprise a heteroalkyl group. "Heteroalkyl" is as described for "alkyl" wherein at least one C atom is substituted by an N, S or O atom. "Heteroalkyl" may include linear, branched and / or cyclic moieties. In certain embodiments, a "lower alkyl" is an alkyl group having 1-6 carbon atoms (i.e., a C1-C6 alkyl). In specific instances, a "lower alkyl" may be linear or branched.

[0245] In some embodiments, lipid derivatives may include aryl groups. In some aspects, lipid derivatives may be aryl groups. "Aryl" refers to a group derived from an aromatic monocyclic or aromatic polycyclic hydrocarbon ring system by removing hydrogen atoms from ring carbon atoms. An aromatic monocyclic or aromatic polycyclic hydrocarbon ring system contains only hydrogen and carbon, with 5 to 18 carbon atoms, wherein at least one ring in the ring system is aromatic, i.e., according to Hückel theory, the ring contains a cyclic delocalized (4n+2) p electron system. The ring system from which aryl groups are derived includes groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. In some embodiments, the term "aryl" may refer to an aromatic ring in which each atom forming the ring is a carbon atom. The aryl ring may be formed by five, six, seven, eight, nine, or more than nine carbon atoms. The aryl group in a lipid may be optionally substituted. Aryl groups include, but are not limited to, phenyl, naphthyl, phenanthrenyl, anthracenyl, fluorenyl, and indenyl. Depending on the structure, an aryl group can be a monoradical or a diradical (ie, an arylene group).

[0246] In some embodiments, lipid derivatives can include heteroaryl moieties." heteroaryl " refers to a group derived from a 3 to 12 yuan aromatic ring group, which includes 2 to 11 carbon atoms and at least one heteroatom, wherein each heteroatom can be selected from N, O and S. As used herein, heteroaryl rings can be selected from monocyclic or bicyclic and fused or bridged ring system rings, wherein at least one ring in the ring system is aromatic, i.e., according to Huckel theory, the ring contains cyclic delocalized (4n+2) p electron systems. One or more heteroatoms in the heteroaryl group can be optionally oxidized. In some embodiments, lipid derivatives can include one or more nitrogen atoms, if present, which are optionally quaternized. Heteroaryl can be connected to the rest of the molecule by any atom of heteroaryl (as long as valence number allows) such as the carbon or nitrogen atom of heteroaryl.Heteroaryl groups include, but are not limited to, azaquinone, acridinyl, benzimidazolyl, benzindolyl, 1,3-benzodioxolanyl, benzofuranyl, benzoxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxolanyl, benzo[b][1,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolanyl, benzodioxinyl, benzopyranyl, benzopyrone, benzofuranyl, benzofuranone, benzothiophenyl (benzothienyl), benzothieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazole yl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-c]pyridazinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, furano[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocyclooctane[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocyclooctane[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocyclooctane[d]pyridinyl, isothiazolyl, imidazolyl , indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolyl, isoquinolinyl, indolizinyl, isoxazolyl, 5,8-methylene-5,6,7,8-tetrahydroquinazolinyl, naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[h]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d] Pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pyridinyl, and phenylthio (i.e., thienyl). "X-membered heteroaryl" refers to the number of ring atoms in the ring, i.e., X. For example, a 5-membered heteroaromatic ring or a 5-membered aromatic heterocyclic ring has 5 atoms in the ring, for example, triazole, oxazole, thiophene, and the like.

[0247] In some embodiments, the term "heteroaryl," when used without the "substituted" modifier, refers to a monovalent group having an aromatic carbon atom or nitrogen atom as the point of attachment, said carbon atom or nitrogen atom forming part of an aromatic ring structure, wherein at least one ring atom is nitrogen, oxygen, or sulfur, and wherein the monovalent group contains no atoms other than carbon, hydrogen, aromatic nitrogen, aromatic oxygen, and aromatic sulfur. Non-limiting examples of heteroaryl groups include acridinyl, furanyl, imidazoimidazolyl, imidazopyrazolyl, imidazopyridinyl, imidazopyrimidinyl, indolyl, indazolinyl, methylpyridinyl, oxazolyl, phenylimidazolyl, pyridinyl, pyrrolyl, pyrimidinyl, pyrazinyl, quinolinyl, quinazolinyl, quinoxalinyl, tetrahydroquinolinyl, thienyl, triazinyl, pyrrolopyridinyl, pyrrolopyrimidinyl, pyrrolopyrazinyl, pyrrolotriazinyl, pyrroloimidazolyl, chromenyl (wherein the point of attachment is one of the aromatic atoms), and chromenyl (wherein the point of attachment is one of the aromatic atoms). Substituted heteroaryl refers to a monovalent group having an aromatic carbon atom or nitrogen atom as the point of attachment, said carbon atom or nitrogen atom forming part of an aromatic ring structure, wherein at least one ring atom is nitrogen, oxygen or sulfur, and wherein the monovalent group further has at least one atom independently selected from the group consisting of non-aromatic nitrogen, non-aromatic oxygen, non-aromatic sulfur F, Cl, Br, I, Si and P.

[0248] In some embodiments, any part of lipid can be substituted. The term "substituted" refers to a portion with a substituent that replaces one or more carbons in the structure or a hydrogen on a substitutable heteroatom (e.g., NH). It should be understood that "replacement" or "substituted" includes implicit conditions, such that such substitutions meet the allowed valence of the substituted atom and the substituent, and the substitution results in a stable compound, i.e., a compound that does not spontaneously undergo transformation (such as by rearrangement, cyclization, elimination, etc.). In certain embodiments, substituted refers to a portion with a substituent that replaces two hydrogen atoms on the same carbon atom, such as replacing two hydrogen atoms on a single carbon with an oxo group, an oxy-group, or a thio-oxo group. As used herein, the term "substituted" is intended to include all permissible substituents of an organic compound. In a broad sense, permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of an organic compound. For appropriate organic compounds, permissible substituents can be one or more and the same or different. For purposes of this disclosure, the heteroatoms (such as nitrogen) may have hydrogen substituents and / or any permissible substituents of organic compounds described herein that satisfy the valences of the heteroatoms. In some embodiments, the substituents may include any of the substituents described herein, for example, halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -ORa 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2. -R b -N(R a )2. -R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2. -R b -OR c -C(O)N(R a )2. -R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (wherein t is 1 or 2); and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl and heteroarylalkyl, any of which may be optionally substituted by alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2. -Rb -N(R a )2. -R b -C(O)R a 、-R b -C(O)OR a 、-R b -C(O)N(R a )2. -R b -OR c -C(O)N(R a )2. -R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (wherein t is 1 or 2) substituted; wherein each R a are independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl or heteroarylalkyl, wherein each R a (If valence permits, the group may be optionally replaced by an alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO2), imino (=NH), oxime (=N-OH), hydrazine (=N-NH2), -R b -OR a 、-R b -OC(O)-R a 、-R b -OC(O)-OR a 、-R b -OC(O)-N(R a )2. -R b -N(R a )2. -R b -C(O)R a 、-R b -C(O)OR a、-R b -C(O)N(R a )2. -R b -OR c -C(O)N(R a )2. -R b -N(R a )C(O)OR a 、-R b -N(R a )C(O)R a 、-R b -N(R a )S(O) t R a (where t is 1 or 2), -R b -S(O) t R a (where t is 1 or 2), -R b -S(O) t OR a (where t is 1 or 2) and -R b -S(O) t N(R a )2 (wherein t is 1 or 2); and wherein each R b are independently selected from a direct bond or a straight or branched alkylene, alkenylene or alkynylene chain, and each R c is a straight or branched alkylene, alkenylene or alkynylene chain.

[0249] In some embodiments, the lipids of the present disclosure can be modified. Modifications can be made to change the properties of the lipids and / or compositions of the present disclosure. For example, modifications can be made to enhance specificity for, for example, a particular target tissue, to alter efficacy, to improve absorption rate and extent, to reduce toxicity, or to alter physical or chemical properties (e.g., solubility) to provide desired characteristics.

[0250] In some embodiments, lipids of the present disclosure can be modified to include polar functional groups, such as alcohols, amines, amides, carboxylic acids, sulfonic acids, and phosphate groups, which can be ionized or capable of generating relatively strong intermolecular attractions (hydrogen bonding) with water. In some embodiments, weakly polar groups (such as carboxylates, aryl halides, and alkyl halides) can be incorporated into lipids of the present disclosure to enhance lipid solubility.

[0251] In some embodiments, the lipids of the present disclosure can be modified to include reversibly and irreversibly linked groups. For example, groups directly bound to the lipid carbon backbone via C—C, C—O, and C—N bonds tend to be irreversible. Alternatively, groups attached to the lipid via ester, amide, phosphate, sulfate, and glycosidic bonds may generally be more reversible.

[0252] In some embodiments, compositions of the present disclosure can include bioactive lipids. In some embodiments, compositions of the present disclosure can be used to transport bioactive lipids from one site to another site. In some embodiments, compositions of the present disclosure can be used to transport bioactive lipids from one site of a subject to another site of a subject.

[0253] Lipids can include fats, waxes, steroids, cholesterol, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, phospholipids, sphingolipids, glycolipids, cationic or anionic lipids, derivatized lipids, etc. In some embodiments, lipids can form micelles, monolayers, and bilayer membranes. In some embodiments, lipids can be combined with other components to self-assemble into lipoprotein systems.

[0254] In some embodiments, the lipid may comprise one or more hydrophobic groups. As used herein, the term "hydrophobic group" refers to a chemical moiety that is insoluble in water or repelled by water. Hydrophobic groups include, but are not limited to, long-chain alkanes and fatty acids, fluorocarbons, silicones, certain steroids (such as cholesterol), and polymers (including, for example, polystyrene and polyisoprene). In some embodiments, the lipid may comprise one or more hydrophilic groups. As used herein, the term "hydrophilic group" refers to a chemical moiety that is soluble in water or attracted to water. Hydrophilic groups include, but are not limited to, alcohols, short-chain carboxylic acids, quaternary amines, sulfonates, phosphates, sugars, and certain polymers, such as polyethylene glycol (PEG). In some embodiments, the lipid may be an amphiphilic compound. As used herein, the term "amphiphilic compound" refers to a compound that has both a hydrophobic portion and a hydrophilic portion. For example, an amphiphilic compound may have a hydrophilic face and a hydrophobic face. Amphiphilic compounds include, but are not limited to, bile acid and bile acid analogs and derivatives, and cholesterol formate. In some embodiments, the compositions of the present disclosure comprise toxic lipid substances. In some embodiments, the compositions of the present disclosure include protective lipid substances. In some embodiments, bioactive lipids include polyunsaturated fatty acids, fat-soluble antioxidants, cholesterol esters or triglycerides, or any combination thereof. In some embodiments, the compositions of the present disclosure include phospholipids, such as 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), plasmalogens, free cholesterol, cholesterol esters (such as cholesterol oleate), triglycerides (such as triolein) etc. In some embodiments, the compositions of the present disclosure include plasmalogens. In some embodiments, the compositions of the present disclosure include free cholesterol. In some embodiments, the compositions of the present disclosure include cholesterol esters. In some embodiments, cholesterol ester is cholesterol oleate. In some embodiments, the compositions of the present disclosure include triglycerides. In some embodiments, triglycerides can be triolein.

[0255] In some embodiments, lipids provide a membrane environment that can dissolve cholesterol. In some embodiments, cholesterol can be actively discharged by the ABC transporter family. In some embodiments, cholesterol can be passively absorbed from cell membranes and / or lipid-rich fragments. In some embodiments, passive absorption of lipid-rich fragments can reduce microglial activation or neuroinflammation. For example, in some embodiments, microglial cells that engulf lipid-rich fragments may be filled with lipid droplets, including lipid droplets rich in cholesterol esters. In some embodiments, exogenous lipoproteins stimulate microglial cholesterol efflux to enhance the phagocytic ability of microglial cells. In some embodiments, the relative affinity of lipoproteins to the extracellular matrix and receptors can adjust the balance between cholesterol efflux (lipid removal) and lipid delivery. In some embodiments, cholesterol can be transported between cells (for example, effluxed from astrocytes and delivered to neurons or oligodendrocytes) to promote cell membrane growth, myelination / remyelination, synaptogenesis, and vesicle release. In some embodiments, another lipid delivered to the cell, including phospholipids, cholesterol esters, and triglycerides, can provide an energy source and change the metabolic state of the recipient cell. In some embodiments, delivery of lipid species having monounsaturated fatty acyl chains (e.g., oleic acid) as well as deuterated polyunsaturated fatty acyl chains (e.g., DHA deuterated at the diallyl position, see Yang et al. (PNAS, 2016, 113(34):E4966-E4975), the contents of which are incorporated herein by reference) can protect cells from oxidative stress and cell death.

[0256] Compositions of the present disclosure can include cationic lipids, zwitterionic lipids, neutral lipids and anionic lipids. Suitable lipids can include fats, waxes, steroids, cholesterol, fat-soluble vitamins, monoglycerides, diglycerides, phospholipids, sphingolipids, glycolipids, cationic or anionic lipids, derivatized lipids, etc. In some embodiments, the lipid can be a phospholipid, a lysolipid, cholesterol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol and a PEGylated lipid.

[0257] In some embodiments, phospholipids include, but are not limited to, phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), and phosphatidylinositol (PI), dimyristoylphosphatidylcholine (DMPC), distearoylphosphatidylcholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dimyristoylphosphatidylglycerol (DMPG), distearoylphosphatidylglycerol (DSPG), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dimyristoylphosphatidylserine (DMPS), distearoylphosphatidylserine (DSPS), dioleoylphosphatidylserine (DOPS), dipalmitoylphosphatidylserine (DPPS), dioleoylphosphatidyl In some embodiments, the phospholipid may be a lysolipid, which contains only one fatty acid moiety bonded to a glycerol subunit via an ester linkage. In some embodiments, lipid extracts such as egg PC, heart extract, brain extract, liver extract, and soybean PC are also contemplated. In some embodiments, the lipids may include derivatized lipids such as PEGylated lipids. In some embodiments, the derivatized lipids may include, for example, DSPE-PEG2000, cholesterol-PEG2000, DSPE-polyglycerol, or other derivatives generally known in the art.

[0258] In some embodiments, the compositions of the present disclosure may include steroids characterized by the presence of a fused tetracyclic nonane ring system. Steroids include, but are not limited to, cholesterol, bile acid, progesterone, cortisone, aldosterone, estradiol, testosterone, and dehydroepiandrosterone. In some embodiments, synthetic steroids and derivatives thereof are also contemplated. Compositions as described herein may contain cationic lipids, which contain positively charged functional groups under physiological conditions. Cationic lipids include, but are not limited to, N, N-dioleyl-N, N-dimethylammonium chloride (DODAC), N, N-distearyl-N, N-dimethylammonium bromide (DDAB), N-(1-(2,3-dioleoyloxy)propyl)-N, N, N-trimethylammonium chloride (DOTAP), N-(1-(2,3-dioleyloxy)propyl)-N, N, N-trimethylammonium chloride (DOTMA), N-[1-(2,3,-ditetradecyloxy)propyl] ... The following were used as the raw materials: N-[1-(2,3, dioleyloxy)propyl]-N,N-dimethyl-N-hydroxyethylammonium bromide (DMRIE), N-[1-(2,3, dioleyloxy)propyl]-N,N-dimethyl-N-hydroxyethylammonium bromide (DORIE), 3β-[N—(N′,N′-dimethylaminoethane)carbamoyl]cholesterol (DC-Chol), dimethyldioctadecylammonium (DDAB), and N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA).

[0259] Compositions as described herein can include anionic lipids containing a diacylglycerol backbone connected to a phosphate group and a net negative charge. Anionic lipids include, but are not limited to, phosphatidic acid, phosphatidylglycerol (PG), phosphatidylserine (PS), phosphoinositides, phosphatidylinositol, phosphatidylinositol-4-phosphate (PtdIns(4)P), phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3), and cardiolipin.

[0260] In some embodiments, compositions as described herein may include lipids, for example, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine (DMPC), 1-tetradecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine (MPPC), 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), 1,2-diphexadecanoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DSPG), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG), 1-tetradecanoyl-2-hexadecanoyl-sn-glycero-3-phosphoglycerol (MPPG) and cholesterol. In some embodiments, compositions as described herein may include neutral lipids. In some embodiments, neutral lipid can be any lipid, including simple lipid, complex lipid and derived lipid.Neutral lipid includes but is not limited to phospholipid, glyceroglycolipid, sphingolipid, sphingoid and sterol.For example, the example of phospholipid includes natural phospholipid or synthetic phospholipid, such as phosphatidylcholine (for example, soybean phosphatidylcholine, egg yolk phosphatidylcholine (EPC), distearoylphosphatidylcholine (DSPC), dipalmitoylphosphatidylcholine (DPPC), palmitoyloleoylphosphatidylcholine (POPC), dimyristoylphosphatidylcholine (DMPC), dioleoylphosphatidylcholine (DOPC) etc.), phosphatidylethanolamine (for example, distearoylphosphatidylethanolamine (DSPE), dipalmitoylphosphatidylethanolamine (DPPE), dioleoylphosphatidylethanolamine (DOPE), dimyristoylphosphoethanolamine (DMPE), 16-O-monomethyl PE , 16-O-dimethyl PE, 18-1-trans PE, palmitoyloleoyl-phosphatidylethanolamine (POPE), 1-stearoyl-2-oleoyl-phosphatidylethanolamine (SOPE) etc.), glycerophospholipids (e.g., phosphatidylserine, phosphatidic acid, phosphatidylglycerol, phosphatidylinositol, palmitoyloleoylphosphatidylglycerol (POPG), lysophosphatidylcholine etc.), sphingomyelin (e.g., sphingomyelin, ceramide phosphoethanolamine, ceramide phosphoglycerol, ceramide phosphoglycerophosphate etc.), glycerophospholipids, sphingomyelin, natural lecithin (e.g., egg yolk lecithin, soybean lecithin etc.) and hydrogenated phospholipids (e.g., hydrogenated soybean phosphatidylcholine etc.).

[0261] Examples of glyceroglycolipids in neutral lipids include sulforibosylglycerides, diglycosyl diglycerides, digalactosyl diglycerides, galactosyl diglycerides and glycosyl diglycerides. Examples of sphingolipids in neutral lipids include galactosyl cerebrosides, lactosyl cerebrosides and gangliosides. Examples of sphingoids in neutral lipids include sphingosine, icosasphingosine, sphingosine and its derivatives. Examples of sterols in neutral lipids include cholesterol, dihydrocholesterol, lanosterol, β-sitosterol, campesterol, stigmasterol, brassicasterol, ergosterol, fucoxosterol and 3β-[N-(N′, N′-dimethylaminoethyl)carbamoyl] cholesterol (DC-Chol).

[0262] In some embodiments, compositions as described herein can comprise any combination of lipid.In some embodiments, lipid compositions can be customized to influence features such as leakage rate, stability, granularity, zeta potential, protein binding, internal circulation and / or the accumulation in tissue or organ.For example, negativity or positive lipid can be comprised, such as DSPG and / or DOTAP, to influence the surface charge of lipoprotein system as described herein.In some embodiments, lipid compositions can comprise the lipid of approximately ten kinds or still less type, or the lipid of approximately five kinds or still less type, or the lipid of approximately three kinds or still less type.In some embodiments, lipid can comprise at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine or at least ten kinds of different lipids. In some embodiments, the molar percentage (mol %) of a particular type of lipid present can be from about 0% to about 100%, from about 10% to about 100%, from about 20% to about 100%, from about 30% to about 100%, from about 50% to about 100%, from about 60% to about 100%, or from about 70% to 100%, from about 80% to 100%, from about 90% to 100% of the total lipid present in a composition as described herein. In some embodiments, the molar percentage (mol %) of a particular type of lipid present can be from about 0% to about 90%, from about 0% to about 80%, from about 0% to about 70%, from about 0% to about 60%, from about 0% to about 50%, from about 0% to about 40%, or from about 0% to 30%, from about 0% to 20%, from about 0% to 10% of the total lipid present in a composition as described herein.

[0263] In some embodiments, the compositions of the present disclosure comprise lipids. In some embodiments, the compositions of the present disclosure comprise less than 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 lipid substances. In some embodiments, the compositions of the present disclosure comprise 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, or 1-20 lipid substances. In some embodiments, the compositions of the present disclosure comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 lipid substances. In some embodiments, the compositions of the present disclosure comprise at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 lipid species. In some embodiments, the compositions of the present disclosure comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 lipid species.

[0264] fatty acid

[0265] In some embodiments, the lipids of the present disclosure may be fatty acids or derivatives thereof. As used herein, fatty acids refer to carboxylic acids with long-chain hydrocarbon side groups.

[0266] In some embodiments, the fatty acid can be a free fatty acid. In some embodiments, the length of the hydrocarbon side group (or chain) can be about 4 to about 36 carbons. In some embodiments, the lipid of the present disclosure can be a saturated fatty acid, and the saturated fatty acid can include a carbon-carbon single bond. In some embodiments, the lipid of the present disclosure can be an unsaturated fatty acid, and the unsaturated fatty acid can include one or more carbon-carbon double bonds. In some embodiments, the unsaturated fatty acid can be a monounsaturated fatty acid containing a carbon-carbon double bond. In some embodiments, the lipid of the present disclosure can be a polyunsaturated fatty acid containing at least two carbon-carbon double bonds. Non-limiting examples of saturated fatty acids include lauric acid, myristic acid, palmitic acid and / or stearic acid. Non-limiting examples of monounsaturated fatty acids include palmitoleic acid, oleic acid, crotonic acid, myristoleic acid, palmitoleic acid, sapienic acid, elaidic acid, vaccenic acid, gadoleic acid, eicosenoic acid, erucic acid and / or nervonic acid. Non-limiting examples of polyunsaturated fatty acids include linolenic acid, linoleic acid, eicosadienoic acid, docosadienoic acid, pinolenic acid, eleostearic acid, melisic acid, eicosatrienoic acid, stearidonic acid, arachidonic acid, eicosatetraenoic acid, adrenic acid, persic acid, eicosapentaenoic acid, ozubondo acid, sardinic acid, lignopentaenoic acid, cervonic acid, and / or arachidonic acid.

[0267] In one embodiment, the fatty acid is an omega-3 fatty acid. In some embodiments, the omega-3 fatty acid is docosahexaenoic acid (DHA). In another embodiment, the omega-3 fatty acid is eicosapentaenoic acid (EPA).

[0268] wax

[0269] In some embodiments, the lipids of the present disclosure may be or may include waxes. As used herein, waxes may refer to long-chain (approximately C) 14 to about C 36 ) saturated or unsaturated fatty acids and long chain (C 16 to about C 30 Waxes may be insoluble in water and / or may be solid at biological temperatures. Examples of waxes are beeswax and cetyl palmitate.

[0270] Triglycerides

[0271] In some embodiments, the lipids of the present disclosure may be or may include triacylglycerols. As used herein, the term "triacylglycerols" refers to molecules containing three fatty acids, each of which forms an ester linkage with a single glycerol.

[0272] Triacylglycerols can contain the same fatty acid at all three positions (also known as simple triacylglycerols) or can contain two or three different fatty acids.

[0273] Glycerophospholipids

[0274] In some embodiments, the lipids of the present disclosure may be or may include glycerophospholipids. As used herein, glycerophospholipids may refer to lipids in which two fatty acids are attached to the first and second carbons of glycerol via ester linkages, and a highly polar or charged group is attached to the third carbon of glycerol via a phosphodiester linkage. The fatty acids in the glycerophospholipids may be any known fatty acids.

[0275] The lipids of the present disclosure may be represented by formula (I):

[0276]

[0277] in:

[0278] X 1 and X 2 are independently N, O or absent; and

[0279] R 1 and R 2 is independently optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, or absent.

[0280] The glycerophospholipid may be phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine or phosphatidylglycerol.

[0281] In some embodiments, the glycerophospholipid may be phosphatidic acid, wherein the group attached to the phosphorus atom in the glycerophospholipid is a hydroxyl group. In some embodiments, the phosphorus-containing atom in the glycerophospholipid may be phosphatidylethanolamine, wherein the group attached to the phosphorus atom in the glycerophospholipid may be ethanolamine. In some embodiments, the glycerophospholipid may be phosphatidylcholine, wherein the group attached to the phosphorus atom in the glycerophospholipid may be choline. In some embodiments, the glycerophospholipid may be phosphatidylglycerol, wherein the group attached to the phosphorus atom in the glycerophospholipid may be glycerol. In some embodiments, the glycerophospholipid may be phosphatidyl 4-5-bisphosphate, wherein the group attached to the phosphorus atom in the glycerophospholipid may be inositol 4,5-bisphosphate. In some embodiments, the glycerophospholipid may be cardiolipin, wherein the group attached to the phosphorus atom in the glycerophospholipid may be phosphatidylglycerol.

[0282] In some embodiments, the glycerophospholipids may be ether lipids or ether-linked lipids, which may have an alkyl chain attached to the first carbon position via an ether bond. The moiety attached to the phosphate group in the ether lipids may be choline, ethanolamine, inositol, or serine. In mammals, ether lipids may comprise approximately 20% of the total phospholipid pool, but tissue distribution varies. Levels are highest in the brain, heart, spleen, and white blood cells.

[0283] Glycerol phospholipids can be derivatives of phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine or phosphatidylglycerol. In some embodiments, lipids can be derivatives of phosphatidylcholine. Phosphatidylcholine can be represented by formula (Ia):

[0284]

[0285] (Ia)

[0286] Derivatives of phosphatidylcholine include 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or POPC); 1,2-di-tetradecanoyl-sn-glycero-3-phosphocholine (1,2-dimyristoyl-sn-glycero-3-phosphocholine or DMPC); 1,2-di-hexadecanoyl-sn-glycero-3-phosphocholine (dipalmitoylphosphatidylcholine or DPPC); 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (dioleoylphosphatidylcholine or DOPC); 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-O-(1Z-tetradecenyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-dodecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine; 1-tridecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(14-pentadecanoyl)-sn-glycero-3-phosphocholine; 1-heneicosanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1,2-di-octadecanoyl-sn-glycero-3- Phosphocholine; 1-(6Z,9Z,12Z,15Z-heneicosatetraenoyl)-sn-glycero-3-phosphocholine; 1,2-didecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-decanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-decanoyl-2-nonadecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-undecanoyl-2-heptadecanoyl-sn-glycero-3-phosphocholine; 1 -Undecanoyl-2-nonadecanoyl-sn-glycero-3-phosphocholine; 1-Undecanoyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-Undecanoyl-2-tricosanoyl-sn-glycero-3-phosphocholine; 1-Undecanoyl-2-pentacosanoyl-sn-glycero-3-phosphocholine; 1-Dodecanoyl-sn-glycero-3-phosphocholine; 1,2-Di-dodecanoyl-sn-glycero-3-phosphocholine; 1-Dodecanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-Dodecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-Dodecanoyl-2-acetyl-sn-glycero-3-phosphocholine;1-Dodecanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-Dodecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-Dodecanoyl-2-tricosanoyl-sn-glycero-3-phosphocholine; 1-Dodecanoyl-2-tetracosanoyl-sn-glycero-3-phosphocholine; 1-Tridecanoyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-Tridecanoyl-2-heptadecanoyl-sn-glycero-3-phosphocholine; 1-Tridecanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-Tridecanoyl-2-heneicosanoyl sn-glycero-3-phosphocholine; 1-tridecanoyl-2-tricosanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-dodecanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9 sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-acetyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(4Z,7Z,1 1-Hexadecanoyl-2-(2E,4E,12E,14E-hexadecanoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(2E,4E,12E,14E-hexadecanoyl)-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine; 1,2-dipentadecanoyl-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-heptadecanoyl-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-nonadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(2E,4E,12E,14E-hexadecatetraenoyl)-sn-glycero-3-phosphocholine;1-Hexadecanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-Hexadecanoyl-2-(6E-octadecenoyl)-sn-glycero-3-phosphocholine; 1-Hexadecanoyl-2-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-Hexadecanoyl-2-(9E-octadecenoyl)-sn-glycero-3-phosphocholine; 1-Hexadecanoyl-2-(10E,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-Hexadecanoyl-2-(9E,11Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-Hexadecanoyl-2-(9E,12E-octadecadienoyl)-sn-glycero-3-phosphocholine n-Glycerol-3-phosphocholine; 1-hexadecanoyl-2-(9Z,11E,13E,15Z-octadecatetraenoyl)-sn-glycerol-3-phosphocholine; 1-hexadecanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycerol-3-phosphocholine; 1-hexadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycerol-3-phosphocholine; 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosapentaenoyl)-sn-glycerol-3-phosphocholine; 1-hexadecanoyl-2-docosanoyl-sn-glycerol-3-phosphocholine; 1-hexadecanoyl-2-(7Z,10Z,1 3Z,16Z-docosatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(8E,11E,14E,17E,20E-tricosapentaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(5Z,9Z-hexacosadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-propionyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(2E-propionyl)-sn-glycero-3-phosphocholine Base; 1-hexadecanoyl-2-(4E-pentanoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-hexanoyl-sn-glycero-3-phosphocholine; 1-(2Z-hexadecenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9E-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine;1-heptadecanoyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-decanoyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-undecanoyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-acetyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-tricosanoyl-sn- Glycerol-3-phosphocholine; 1-heptadecanoyl-2-nonanoyl-sn-glycerol-3-phosphocholine; 1,2-bis-(9Z,12Z-heptadecadienyl)-sn-glycerol-3-phosphocholine; 1-octadecanoyl-2-tetradecanoyl-sn-glycerol-3-phosphocholine; 1-octadecanoyl-2-(9Z-hexadecenoyl)-sn-glycerol-3-phosphocholine; 1-octadecanoyl-2-(11Z-octadecenoyl)-sn-glycerol-3-phosphocholine; 1-octadecanoyl-2-(13Z-octadecenoyl)-sn-glycerol-3-phosphocholine; 1-octadecanoyl-2-(9E-octadecenoyl)-sn-glycerol-3-phosphocholine; 1-octadecanoyl Acyl-2-(6Z,9Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(9E,11E,13E,15E-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-acetyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(13Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(14Z-eicosenoyl)-sn-glycero-3-phosphocholine Choline; 1-octadecanoyl-2-(5Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(5Z,11Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(5Z,8Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(8Z,11Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(5Z,8Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine;1-Octadecanoyl-2-(8Z,10Z,12Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(9Z,11Z,13Z,15Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(9Z,11Z,13Z,15Z,17Z-docosapentaenoyl)-sn-glycero-3-phosphocholine sn-glycero-3-phosphocholine; 1-octadecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-propionyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(2E-propionyl)-sn-glycero-3-phosphocholine; 1,2-bis-(11E-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(11E-octadecenoyl)-2-docosanoyl-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-octadecanoyl-sn-glycero-3-phosphocholine; 1,2-bis-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(1 1Z-octadecenoyl)-2-docosapentaenoyl-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(13Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(14Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(16Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(2Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(5Z-octadecenoyl)-sn-glycero-3-phosphocholine ; 1,2-di-(8Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9E-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(6Z,9Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine;1-(9Z-octadecenoyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-docosanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-tetracosanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-butyryl-sn-glycero-3-phosphocholine; 1-( 2E,4E-octadecadienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(6Z,9Z-octadecadienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1,2-bis-(6Z,9Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9Z,11Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12E-octadecadienoyl)-2-(9Z,11E-heptadecadienyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; -octadecadienoyl)-2-(13Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9E,11E,13E-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine Z,15Z-octadecatrienoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9E,11E,13E,15E-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9Z,11E,13E,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(4Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-undecanoyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine;1-nonadecanoyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-nonanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-dodecanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(7Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(9Z-octadecenoyl)-sn-glycero-3- Phosphocholine; 1-eicosanoyl-2-(8Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(11Z,14Z,17Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-cosanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2- Nonanoyl-sn-glycero-3-phosphocholine; 1,2-bis-(11E-eicosenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(13E-eicosenoyl)-2-docosanoyl-sn-glycero-3-phosphocholine; 1-(9Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-triadecanoyl-sn-glycero-3-phosphocholine; 1-(8E,11E, sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine;1-Henicosanoyl-2-decanoyl-sn-glycero-3-phosphocholine; 1-Henicosanoyl-2-dodecanoyl-sn-glycero-3-phosphocholine; 1-Henicosanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine; 1-Henicosanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1,2-Di-Henicosanoyl-sn-glycero-3-phosphocholine; 1-Docosanoyl-sn-glycero-3-phosphocholine; 1-Docosanoyl-2-decanoyl-sn-glycero-3-phosphocholine; 1-Docosanoyl-2-undecanoyl-sn-glycero-3-phosphocholine; 1-Docosanoyl-2-octadecanoyl-sn-glycero-3 -phosphocholine; 1-docosanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-docosanoyl-2-(12Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-di-docosanoyl-sn-glycero-3-phosphocholine; 1-docosanoyl-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine; 1-docosanoyl-2-cosanoyl-sn-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; sn-glycero-3-phosphocholine; 1-tricosanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1,2-ditricosanoyl-sn-glycero-3-phosphocholine; 1-tetracosanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-tetracosanoyl-2-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-tetracosanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-di-tetracosanoyl-sn-glycero-3-phosphocholine; 1,2-di-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1-pentacosanoyl Acyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-propionyl-sn-glycero-3-phosphocholine; 1,2-dipropionyl-sn-glycero-3-phosphocholine; 1-dotriadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-tetratriadecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-hexatriadecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-butyryl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1,2-dibutyryl-sn-glycero-3-phosphocholine; 1-pentanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine;1-Hexanoyl-sn-glycero-3-phosphocholine; 1-Hexanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-octanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-octanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1,2-dioctanoyl-sn-glycero-3-phosphocholine; 1-nonanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-nonanoyl-2-nonadecanoyl-sn-glycero-3-phosphocholine; 1-nonanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-nonanoyl-2-heneicosanoyl-sn-glycero-3-phosphocholine; 1,2-dinonanoyl-sn-glycero -3-phosphocholine; 1-tetradecyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-tetradecyl-2-acetyl-sn-glycero-3-phosphocholine; 1-tetradecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-pentadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-( 9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(5E,8E,11E,14E-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-propanoyl Acyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(2E-propionyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-hexanoyl-sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-heptadecanyl-2-heptadecanoyl-sn-glycero-3-phosphocholine; 1-heptadecanyl-2-acetyl-sn-glycero-3-phosphocholine; 1-heptadecanyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-heptadecanyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine;1-Heptadecanyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-octadecyl-2-formyl-sn-glycero-3-phosphocholine; 1-octadecyl-2-(9Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-octadecyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-octadecyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-octadecyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-nonadecanyl-2-docosanoyl-sn-glycero-3-phosphocholine; 2-tetradecanoyl-sn-glycero-3-phosphocholine Choline; 2-octadecanoyl-sn-glycero-3-phosphocholine; 2-(9E-octadecenoyl)-sn-glycero-3-phosphocholine; 2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 2-(2E-propionyl)-sn-glycero-3-phosphocholine; 2-butyryl-sn-glycero-3-phosphocholine; 2-pentanoyl-sn-glycero-3-phosphocholine; 2-hexanoyl-sn-glycero-3-phosphocholine; 2-heptanoyl-sn-glycero-3-phosphocholine; 1-(9E-decenyl)-sn-glycero-3-phosphocholine; 1-(1Z-tetradecenyl)-sn-glycero-3-phosphocholine; 1-pentadecyl-sn-glycero-3-phosphocholine; 1-hexadecane sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenyl)-sn-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-sn-glycero-3-phosphocholine; 1-nonadecanyl-sn-glycero-3-phosphocholine; 1-pentyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(7Z-hexadecenoyl)-2-(4Z,7Z,10Z,13Z, 16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-acyl-sn-glycero-3-phosphocholine; 1-(6-[5]-ladder-hexyl)-2-(8-[3]-ladder-octyl)-sn-glycerophosphocholine; 1-(8-[5]-ladder-octyl)-2-(8-[3]-ladder-octyl)-sn-glycerophosphocholine; 1-(8-[3]-ladder-octyl)-2-(8-[3]-ladder-octyl)-sn-glycerophosphocholine; 1-hexadecyl-2-(8-[3]-ladder-octyl)-sn-glycerophosphocholine; 1-(6-[5]-ladder-hexanoyl)-2-(8-[3]-ladder-octyl)-sn-glycerophosphocholine;1-(8-[5]-ladderane-octanoyl)-2-(8-[3]-ladderane-octyl)-sn-glycerophosphocholine; 1-(6-[3]-ladderane-hexanoyl)-2-(8-[3]-ladderane-octyl)-sn-glycerophosphocholine; 1-(8-[3]-ladderane-octanoyl)-2-(8-[3]-ladderane-octyl)-sn-glycerophosphocholine; 1-tetradecanoyl-2-(8-[3]-ladderane-octyl)-sn-glycerophosphocholine; 1-(9E-decenyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(10E-octadecenyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-(5Z,8Z,11Z ,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(2E,6E-phytadienyl)-2-(2E,6E-phytadienyl)-sn-glycero-3-phosphocholine; 1-(2E,6E,10E-phyttrienyl)-2-(2E,6E10E-phyttrienyl)-sn-glycero-3-phosphocholine; 1-(2E-phytenyl)-2-(2E-phytenyl)-sn-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(4Z,7 Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-pentadecanoyl-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z-heptadecanoyl)-glycero-3 -phosphocholine; 1-dodecanoyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-heneicosanoyl-glycero-3-phosphocholine; 1-tridecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-tridecanoyl-2-(9Z,12Z-heptadecadienyl)-glycero-3-phosphocholine;1-Tridecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(9Z-nonadecaenoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(11Z-docoenoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(13Z,16Z-eicosenoyl)- 1-Tetradecanoyl-2-tridecanoyl-glycero-3-phosphocholine; 1-Tetradecanoyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-Tetradecanoyl-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-Tetradecanoyl-2-nonadecenoyl-glycero-3-phosphocholine; 1-Tetradecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-Tetradecanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-Tetradecanoyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-Tetradecanoyl-2-(13 Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z-heptadecanoyl) -glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine;1-(9Z-tetradecenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-tetradecanoyl-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z-tetradecenoyl)-glycero -3-phosphocholine; 1-pentadecanoyl-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(11Z-eicosanoyl) 1-Pentadecanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-Pentadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-Pentadecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-Pentadecanoyl-2-docosaenoyl-glycero-3-phosphocholine; 1-Pentadecanoyl-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-Pentadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)- )-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-pentadecenoyl-glycero-3-phosphocholine; 1,2-di-(9Z-pentadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine;1-(9Z-pentadecenyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-(9Z,12Z,15Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-(9Z,12Z,15Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-(8Z,11Z,14Z-eicostrienoyl)-glycero-3-phosphocholine; -(9Z-pentadecenyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-henicosanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-hexadecanoyl-2-tridecanoyl-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-hexadecanoyl 1-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-hexadecanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-hexadecanoyl-2-(11Z-docosadienoyl)-glycero-3-phosphocholine; 1-hexadecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl) -2-(9Z-pentadecenoy)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine;1-(9Z-hexadecenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-heptadecanoyl-2-( 9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-henicosanoyl-glycero-3-phosphocholine; 1-heptadecanoyl-2-docosanoyl-glycero-3-phosphocholine; 1-heptadecanoyl-2-(11Z-docosanoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-(9Z-hexadecenoyl)- Glycerol-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-heptadecanoyl-glycerol-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycerol-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycerol-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycerol-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(11Z-eicosenoyl)-glycerol-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-heneicosanoyl-glycerol-3- Phosphocholine; 1-(9Z-heptadecanoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-(7Z,10Z,13Z,16Z-docosetraenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine;1-(9Z,12Z-heptadecadienoyl)-2-(9Z-pentadecadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(6Z,9Z,12Z-octadecadienoyl)- 1-(9Z,12Z-heptadecadienoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(5Z,8Z,11Z, 1-(9Z,12Z-heptadecadienoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-tridecanoyl-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z,12Z,15Z-octadecadienoyl)-glycero Oil-3-phosphocholine; 1-octadecanoyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-heneicosanoyl-glycero-3-phosphocholine; 1-octadecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine;1-(9Z-octadecenoyl)-2-henicosanoyl-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(11Z-docosadienoyl)-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(13Z,16Z-docosadienoyl)-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-dodecanoyl-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(9Z-pentadecenoyl)-3-phosphocholine Choline; 1-(9Z,12Z-octadecadienoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(9Z,12Z,15Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)- 2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z -pentadecanoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-eicosanoyl-glycero-3-phosphocholine;1-(6Z,9Z,12Z-octadecatrienoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero -3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3- Phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; (9Z,12Z,15Z-octadecatrienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-henicosanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(7Z,10Z,13Z,16Z-docosetraenoyl)-glycero-3-phosphocholine;1-(9Z,12Z,15Z-octadecatrienoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-heptadecanoyl-glycero-3 -phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z- Nonadecanoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(11Z-docosadienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; Nonadecanoyl-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-eicosanoyl-glycero-3-phosphocholine; 1-nonadecanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine;1-Nonadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-Nonadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-Nonadecanoyl-2-docosanoyl-glycero-3-phosphocholine; 1-Nonadecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-Nonadecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-Nonadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)- Glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(9Z-tetradecenoyl)-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-pentadecanoyl-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(9Z-hexadecenoyl)-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(9Z-heptadecanoyl)-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(9Z,12Z-heptadecanoyl)-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-octadecanoyl-glycerol-3-phosphocholine Choline; 1-(9Z-nonadecaenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecaenoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecaenoyl)-2-(6Z,9Z,12Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecaenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecaenoyl)-2-nonadecaenoyl-glycero-3-phosphocholine; 1-(9Z-nonadecaenoyl)-2-(11Z-eicosadienoyl)- Glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosopentaenoyl)-glycerol-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-docosanoyl-glycerol-3-phosphocholine; 1-eicosanoyl-2-(9Z-tetradecenoyl)-glycerol-3-phosphocholine; 1-eicosanoyl-2-pentadecanoyl-glycerol-3-phosphocholine; 1-eicosanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycerol-3-phosphocholine;1-eicosanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-dodecanoyl-glycero-3-phosphocholine 1-(11Z-eicosenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)- 2-Octadecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(5Z,8Z,11Z,14Z- 1-(11Z-eicosenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosopentaenoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-heneisconoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine;1-(11Z,14Z-eicosadienoyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(9Z,12Z-heptadecenyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)- 2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(11Z-eicosatetraenoyl)- -3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; -(8Z,11Z,14Z-eicosatrienoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(11Z-eicosanoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-heneicosanoyl-glycero-3-phosphocholine;1-(8Z,11Z,14Z-eicosatrienoyl)-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine Choline; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl) 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(11Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(5Z ,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-henicosanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-dodecanoyl-glycero-3-phosphocholine;1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-tridecanoyl-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-pentadecanoyl-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z-pentadecanoyl)-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z-hexadecenoyl)-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z-heptadecanoyl)-3-phosphocholine 3-Phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z-nonadecaenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-hexadecanoyl-glycero-3-phosphocholine; 1-henicosanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-henicosanoyl-2-(9Z,12Z-heptadecanoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-henicosanoyl 1-Henicosanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(9Z-nonadecaenoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(8Z,11Z,14Z-eicosatoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(11Z-docoenoyl)-glycero-3-phosphocholine; 1-docoesoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine;1-Docosanoyl-2-pentadecanoyl-glycero-3-phosphocholine; 1-Docosanoyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-Docosanoyl-2-hexadecanoyl-glycero-3-phosphocholine; 1-Docosanoyl-2-(9Z,12Z-heptadecadienyl)-glycero-3-phosphocholine; 1-Docosanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-Docosanoyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-Docosanoyl-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine; 1-Docosanoyl-2-eicosanoyl-glycero-3-phosphocholine; 1 -Docosanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-Docosanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-Docosanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-(11Z-docosenoyl)- )-2-hexadecanoyl-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(9Z-heptadecatetraenoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero Oil-3-phosphocholine; 1-(11Z-docosenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine;1-(13Z,16Z-docosadienoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z-hexadecanoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z-hexadecanoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z,12Z-heptadecanoyl) 1-(13Z,16Z-docosadienoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(11Z-eicosanoyl)-glycero-3-phosphocholine Choline; 1-(13Z,16Z-docosadienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1,2-bis-(13Z,16Z-docosadienoyl)-sn-glycero-3-phosphocholine; 1-(13Z,16Z-heneicosanoyl)- 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine;1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; )-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(11Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(5Z,8Z,11Z,14Z-eicosadienoyl)- 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; -(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine;1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-nonadecanoyl)-glycero-3 -phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-henicosanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-dodecanoyl-glycero-3-phosphocholine; 1-hexadecyl-2-tetradecanoyl-glycero-3-phosphocholine; 1-hexadecyl -2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-pentadecanoyl-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z,12Z-heptadecadienyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(11Z-eicosenoyl)-glycero-3- Phosphocholine; 1-hexadecyl-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-octadecyl-2-tridecanoyl-glycero-3-phosphocholine; 1-octadecyl-2-tetradecanoyl-glycero-3-phosphocholine; 1-octadecyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-octadecyl-2-pentadecanoyl-glycero-3-phosphocholine; 1-octadecyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-octadecyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine;1-Octadecyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-Octadecyl-2-(9Z-nonadecaenoyl)-glycero-3-phosphocholine; 1-Octadecyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-Octadecyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-Octadecyl-2-(8Z,11Z,14Z-eicostrienoyl)-glycero-3-phosphocholine; 1-Octadecyl-2-(11Z-eicosadienoyl)-glycero-3-phosphocholine; 1-Eicosyl-glycero-3-phosphocholine; 1-Eicosyl-2-tridecanoyl-glycero-3-phosphocholine Base; 1-eicosyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-eicosyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-eicosyl-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(11Z,14Z-eicosadienoyl) 1-Eicosyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-Eicosyl-2-henicosanoyl-glycero-3-phosphocholine; 1-Eicosyl-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-Eicosyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-Eicosyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-Eicosyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine Choline; 1-(1Z-hexadecenyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(9Z-heptadecenyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(9Z-heptadecenyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-nonadecanoyl-glycero-3-phosphocholine;1-(1Z-hexadecenyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-heniconadonoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(11Z-docosanoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(13Z,16Z-docosadienoyl)-glycero- 3-Phosphocholine; 1-(1Z-octadecenyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(9Z,1 2Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(11Z-eicosanoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-docosanoyl 1-(1Z-octadecenyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(7Z,10Z,13Z,16Z-docosetetraenoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-pentadecanoyl-glycero-3-phosphocholine;1-(1Z-eicosyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(1Z-eicosyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(1Z-eicosyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(1Z-eicosyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(1Z-eicosyl)-2-(11Z-eicosenoyl) -glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-henicosanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(11Z-docosanoyl)-glycero-3-phosphocholine; 1-decanoyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2 -(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(13Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(13Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine Sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine;1-(11Z-octadecenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(13Z,16Z-docosadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(5Z,8Z,11Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(13Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecadienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecadienoyl)-2-(5Z,8Z,11Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecadienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 9Z,12Z-octadecatrienoyl)-2-(13Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(13Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-(8Z,11Z,14Z,17Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(11Z-eicosanoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine;1-(11Z,14Z-eicosadienoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 5Z,8Z,11Z-eicosatrienoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(11Z-eicosanoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(11Z-eicosanoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(11Z-octadecaenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine ; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docoenoyl)-2-(9Z-tetradecenoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docoenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docoenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(13Z- sn-glycero-3-phosphocholine; 1-(13Z-docoenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docoenoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docoenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(13Z,16Z-docoenoyl)-2-(11Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine;1-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(15Z-tetradecenoyl)-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(15Z-tetradecenoyl)-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-(15Z-tetradecenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(15Z-tetradecenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl) sn-glycero-3-phosphocholine; 1-hexadecyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenyl)-2-docosanoyl-sn-glycero-3-phosphocholine; 1-(11Z-octadecenyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; -glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-docosanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-tetracosanoyl-sn-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-docosanyl-2-(9Z,12Z,15Z-octadecenyl)-2-docosanoyl-sn-glycero-3-phosphocholine sn-glycero-3-phosphocholine; 1-(13Z-docosenyl)-2-(13Z,16Z-docosatrienoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docosenyl)-2-(10Z,13Z,16Z-docosatrienoyl)-sn-glycero-3-phosphocholine; 1-tetracosyl-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(11Z-octadecenyl)-sn-glycero-3-phosphocholine;1-(1Z-octadecadienyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(1Z,9Z-octadecadienyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-(1Z,9Z-octadecadienyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; -(1Z,9Z-octadecadienyl)-2-(13Z-docosaenoyl)-sn-glycero-3-phosphocholine; 1-(1Z,9Z-octadecadienyl)-2-tetracosanoyl-sn-glycero-3-phosphocholine; 1-(1Z,9Z-octadecadienyl)-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn -glycero-3-phosphocholine; 1-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1-(16Z,19Z,22Z,24Z,28Z,31Z-triacontahexanoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(18Z,21Z,24Z,27Z,30Z-triacontahexanoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(21Z,24Z,27Z,30Z-triacontahexanoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine Oleyl-3-phosphocholine; 1-decanoyl-2-dodecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-undecanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-decanoyl-sn-glycero-3-phosphocholine; 1-(4Z-octadecenyl-sn-glycero-3-phosphocholine; 1-(13Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(Z)-en-1-yl-2-acyl-sn-glycero-3-phosphocholine; 1-(1Z-enyl)-sn-glycero-3-phosphocholine; 1-alkyl-2-acyl-sn-glycero-3-phosphocholine;1-Alkyl-sn-glycero-3-phosphocholine; 1-(10Z-heptadecanoyl)-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z-tetradecenoyl)-sn-glycero-3-phosphocholine; 1-(10Z,13Z,16Z-nonadecatrienoyl)-sn-glycero-3-phosphocholine; 1-decanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-docosacanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-tricosanoyl-sn-glycero-3-phosphocholine choline; 1-decanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-decanoyl-2-butyryl-sn-glycero-3-phosphocholine; 1-undecanoyl-sn-glycero-3-phosphocholine; 1,2-di-undecanoyl-sn-glycero-3-phosphocholine; 1-undecanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-undecanoyl-2-heunedecanoyl-sn-glycero-3-phosphocholine; 1-undecanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-dodecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Base; 1-dodecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-dodecanoyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-dodecanoyl-2-cosanoyl-sn-glycero-3-phosphocholine; 1-dodecanoyl-2-cosanoyl-sn-glycero-3-phosphocholine; 1,2-di-tridecanoyl-sn-glycero-3-phosphocholine; 1-tridecanoyl-2-nonadecanoyl-sn-glycero-3-phosphocholine; 1-tridecanoyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(11Z ,14Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9E,11E,13E,15E-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-tetracosanoyl-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1,2-di-(9E-tetradecenoyl)-sn-glycero-3-phosphocholine;1-(9Z-tetradecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9Z-tetradecenoyl)-sn-glycero-3-phosphocholine; 1-pentadecanoyl-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-decanoyl Pentadecanoyl-2-henicosanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-dodecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-heptadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z-heptadecanoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl- 2-(11E-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(11Z,13Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(2Z,4Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(6Z,9Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9E,11E-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9E,11E,13E,15E-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z,11Z,13Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine;1-Hexadecanoyl-2-acetyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(8E,11E,14E-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(5E,8E,11E,14E-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(13Z-docosaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(7 Sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(4E,7E,10E,13E,16E,19E-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(tetracosanoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-butanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-pentanoyl-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-nonanoyl-sn-glycero-3-phosphocholine; 1-(9E-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2 -(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; ,2-bis-(2E,4E-hexadecadienoyl)-sn-glycero-3-phosphocholine; 1-(2E,4E-hexadecadienoyl)-2-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine; 1,2-bis-heptadecanoyl-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-heptadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(10Z-heptadecanoyl)-sn-glycero-3-phosphocholine;1,2-Di-(9Z-heptadecanoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-decanoyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(10E-undecenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-dodecanoyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(2E,4E-hexadecadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(12Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1- Octadecanoyl-2-(16Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(7Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(10Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl) -sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(8Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(5Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(8Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(5Z,11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(13Z-docosanoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(10Z,13Z,16Z-docosatrienoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-sn-glycero-3-phosphocholine;1-Octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-tetracosanoyl-sn-glycero-3-phosphocholine; 1-Octadecanoyl-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1,2-Di-(10Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(13Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1 -(11Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(12Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(15Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(17Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(3Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-( 6E-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(7Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9E-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9E-octadecenoyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(9E-octadecenoyl)-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine;1,2-bis-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(2Z,4Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-octadecanoyl-sn-glycero-3-phosphocholine; 1,2-bis-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1, 2-Di-(9Z,11E,13E-octadecadienoyl)-sn-glycero-3-phosphocholine; 1,2-Di-(9Z,12Z,15Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9E,11E,13E,15E-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-(9E,11E,13E,15E-octadecatetraenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,11E,13E,15Z-octadecatetraenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-dodecanoyl-sn -glycero-3-phosphocholine; 1-nonadecanoyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-decanoyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1,2-di-nonadecanoyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-acetyl-sn-glycero-3-phosphocholine; 1-nonadecanoyl-2-pentacanoyl-sn-glycero-3-phosphocholine; 1-acetyl-sn-glycero-3-phosphocholine; 1-acetyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-acetyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-Acetyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-diacetyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-decanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-undecanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-eicosanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1,2-di-eicosanoyl-sn-glycero-3-phosphocholine;1-Eicosanoyl-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-Eicosanoyl-2-(13Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-Eicosanoyl-2-(5Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-Eicosanoyl-2-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-Eicosanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-Eicosanoyl-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-Eicosanoyl Acyl-2-(15Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(13Z-eicosenoyl)-2-docosanoyl-sn-glycero-3-phosphocholine; 1,2-bis-(9E-eicosenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(9Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(11E,14E-eicosadienoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(5E,8E,11E,14E-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1,2- Di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosopentaenoyl)-sn-glycero-3-phosphocholine; 1-henicosanoyl-sn-glycero-3-phosphocholine; 1-henicosanoyl-2-undecanoyl-sn-glycero-3-phosphocholine; 1-henicosanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-docosanoyl-2-dodecanoyl-sn-glycero-3-phosphocholine; 1-docosanoyl-2-tridecanoyl-sn-glycero-3-phosphocholine; 1-docosanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine Phosphocholine; 1-docosanoyl-2-(13Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-docosanoyl-2-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-docosanoyl-2-(7Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-docosanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-docosanoyl-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-docosanoyl-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(13E-docosenoyl)-sn-glycero-3-phosphocholine;1,2-Bis-(13Z-docosaenoyl)-sn-glycero-3-phosphocholine; 1-(4E,7E,10E,13E,16E,19E-docosahexaenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1,2-Bis-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1,2-Bis-(9Z-tricosenoyl)-sn-glycero-3-phosphocholine; 1-tetracosanoyl-sn-glycero-3-phosphocholine; 1-tetracosanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-tetracosanoyl-2-(11Z-eicosenoyl) -sn-glycero-3-phosphocholine; 1,2-bis-(5E,9E-hexacosadienoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(5E,9Z-hexacosadienoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(5Z,9E-hexacosadienoyl)-sn-glycero-3-phosphocholine; 1-(5Z,9Z-hexacosadienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1,2-bis-(5Z,9Z-hexacosadienoyl)-sn-glycero-3-phosphocholine; 1,2-bis-(6Z,9Z-hexacosadienoyl)-sn-glycero-3-phosphocholine; 1-butyryl-sn-glycero- 3-Phosphocholine; 1-butyryl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1,2-divaleranoyl-sn-glycero-3-phosphocholine; 1,2-dihexanoyl-sn-glycero-3-phosphocholine; 1-hexanoyl-2-octanoyl-sn-glycero-3-phosphocholine; 1,2-di-(2E,4E-hexadienoyl)-sn-glycero-3-phosphocholine; 1-(3E,5E-hexadienoyl)-2-(11E,13E-tetradecadienoyl)-sn-glycero-3-phosphocholine; 1-heptanoyl-sn-glycero-3-phosphocholine; 1-heptanoyl-2-heneicosanoyl-sn-glycero-3-phosphocholine; 1,2-diheptanoyl -sn-glycero-3-phosphocholine; 1-octanoyl-sn-glycero-3-phosphocholine; 1-octanoyl-2-nonadecanoyl-sn-glycero-3-phosphocholine; 1-octanoyl-2-heneicosanoyl-sn-glycero-3-phosphocholine; 1-octanoyl-2-hexanoyl-sn-glycero-3-phosphocholine; 1,2-di-(2E,4E-octadienoyl)-sn-glycero-3-phosphocholine; 1-nonanoyl-sn-glycero-3-phosphocholine; 1-nonanoyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-nonanoyl-2-tricosanoyl-sn-glycero-3-phosphocholine; 1-nonanoyl-2-pentanoyl-sn-glycero-3-phosphocholine;1-Methyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-Methyl-2-acetyl-sn-glycero-3-phosphocholine; 1-dodecyl-2-acetyl-sn-glycero-3-phosphocholine; 1-tetradecyl-2-pentadecanoyl-sn-glycero-3-phosphocholine; 1-tetradecyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-tetradecyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-tetradecyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-tetradecyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-tetradecyl-2-(9Z ,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-tetradecyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-pentadecyl-2-acetyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-formyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-heptadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-nonadecanoyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z-eicosenoyl)-sn-glycero- 3-Phosphocholine; 1-hexadecyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecyl-2-butyryl-sn-glycero-3-phosphocholine; 1-hexadecyl-2-pentanoyl-sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(9Z- sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-heptadecanyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-octadecyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-octadecyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-octadecyl-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-octadecyl-2-acetyl-sn-glycero-3-phosphocholine;1-Octadecyl-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-Octadecyl-2-(5E,8E,11E,14E-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-Octadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-Octadecyl-2-(5Z,8Z,11Z,14Z,17Z-eicosopentaenoyl)-sn-glycero-3-phosphocholine; 1-Octadecyl-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-Octadecyl-2-(7Z,10Z,13Z,16 Sn-glycero-3-phosphocholine; 1-octadecyl-2-propionyl-sn-glycero-3-phosphocholine; 1-octadecyl-2-(2E-propionyl)-sn-glycero-3-phosphocholine; 1-octadecyl-2-butyryl-sn-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-nonadecanyl-2-acetyl-sn-glycero-3-phosphocholine; 1-ethyl-2-acetyl-sn-glycero-3-phosphocholine; 1-eicosyl-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-diphosphocholine Decyl-2-acetyl-sn-glycero-3-phosphocholine; 1-eicosyl-2-docosanoyl-sn-glycero-3-phosphocholine; 1-octyl-2-acetyl-sn-glycero-3-phosphocholine; 2-hexadecanoyl-sn-glycero-3-phosphocholine; 2-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine; 2-acetyl-sn-glycero-3-phosphocholine; 2-propionyl-sn-glycero-3-phosphocholine; 1-tetradecyl-sn-glycero-3-phosphocholine; 1-(1Z-pentadecenyl)-sn-glycero-3-phosphocholine; 1-(11Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(9E-hexadecenoyl)- sn-glycero-3-phosphocholine; 1-(9Z-hexadecenyl)-sn-glycero-3-phosphocholine; 1-heptadecanyl-sn-glycero-3-phosphocholine; 1-(1Z-heptadecenyl)-sn-glycero-3-phosphocholine; 1-octadecyl-sn-glycero-3-phosphocholine; 1-(1Z,9Z-octadecadienyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(7Z-hexadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1,2-diacyl-sn-glycero-3-phosphocholine; 2-acyl-sn-glycero-3-phosphocholine;2-(8-[3]-ladder-octyl)-sn-glycero-3-phosphocholine; 1-(6-[3]-ladder-hexyl)-2-(8-[3]-ladder-octyl)-sn-glycero-3-phosphocholine; 1-(10-methylhexadecyl)-2-(8-[3]-ladder-octyl)-sn-glycero-3-phosphocholine; 1-tetradecyl-2-(8-[3]-ladder-octyl)-sn-glycero-3-phosphocholine; 1-(10E-undecenyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(11Z-hexadecenyl)-2-acetyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(9Z-octadecenyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine sn-glycero-3-phosphocholine; 1-(2E,6E,10E,14E-phytatetraenyl)-2-(2E,6E,10E,14E-phytatetraenyl)-sn-glycero-3-phosphocholine; 1,2-diphytyl-sn-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-(1Z,12Z-nonadecadienyl)-sn-glycero-3-phosphocholine; 2-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z ,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(9Z,12Z,15Z-octadecadienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(11Z,14Z-eicosadienoyl)-glycero- 3-Phosphocholine; 1-dodecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(11Z-docosatrienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-dodecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-tridecanoyl-2-dodecanoyl-glycero-3-phosphocholine; 1-tridecanoyl-2-tetradecanoyl-glycero-3-phosphocholine; 1-tridecanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine;1-Tridecanoyl-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-hexadecanoyl-glycero-3-phosphocholine; 1-Tridecanoyl-2-(9Z-heptadecenyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-octadecanoyl-glycero-3-phosphocholine; 1-Tridecanoyl-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(9Z,12Z,15Z-octadecadienoyl)-glycero-3-phosphocholine; 1-Tridecanoyl-2-(6Z,9Z,12 Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-tridecanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-tridecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-tridecanoyl-2-docosanoyl-glycero-3-phosphocholine; 1-tridecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-tridecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-tetradecanoyl-2- (9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-tetradecanoyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-tetradecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-tetradecanoyl-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-tetradecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-tetradecanoyl-2-heneicosanoyl-glycero-3-phosphocholine; 1-tetradecanoyl-2-(7Z,10Z,1 3Z,16Z-docosetetraenoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-nonadecanoyl-glycero-3-phosphocholine;1-(9Z-tetradecenoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(11Z-docosanoyl)-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl) -2-(7Z,10Z,13Z,16Z-docosetetraenoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-dodecanoyl-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(9Z,12Z-heptadecadienyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-eicosanoyl-glycero-3-phosphocholine; 1-pentadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-pentadecanoyl-2-(13Z,16Z-docosedienoyl)-glycero-3-phosphocholine; 1-pentadecanoyl- 2-(7Z,10Z,13Z,16Z-docosetetraenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(6Z ,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(9Z-pentadenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadenoyl)-2-nonadenoyl-glycero-3-phosphocholine; 1-(9Z-pentadenoyl)-2-(9Z-nonadenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(9Z-pentadenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine;1-(9Z-pentadecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-pentadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-hexadecanoyl-2-(9Z,12Z-heptadecadienyl)-glycero-3-phosphocholine; 1-hexadecanoyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-hexadecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-hexadecanoyl- 2-Henicosanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2 -(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(7Z,10Z,13Z,16Z-docosetetraenoyl)-glycero-3-phosphocholine; -heptadecanoyl-2-dodecanoyl-glycero-3-phosphocholine; 1-heptadecanoyl-2-tetradecanoyl-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-hexadecanoyl-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine;1-heptadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-eicosanoyl-glycero-3-phosphocholine; 1-heptadecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-heptadecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl) 1-(9Z-heptadecanoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecanoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(9Z -heptadecenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(9Z,12Z,15Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(9Z,12Z,15Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(11Z,14Z-eicosadienoyl) choline; 1-(9Z-heptadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-(9Z-heptadecenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine;1-(9Z-heptadecanoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; -(9Z,12Z-heptadecadienoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2 -Henicosanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(11Z-docosanoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-heptadecadienoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-pentadecanoyl-glycero-3-phosphocholine; 1-octadecanoyl-2-heptadecanoyl Acyl-glycero-3-phosphocholine; 1-octadecanoyl-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-octadecanoyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-pentadecanoyl-glycero-3-phosphocholine;1-(9Z-octadecenoyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(9Z-heptadecenyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(9Z,12Z-heptadecadienyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine. 1-(9Z,12Z-octadecadienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-( 9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(11Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-heniconadonoyl-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-docosanoyl-glycero-3-phosphocholine;1-(9Z,12Z-octadecadienoyl)-2-(11Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecadienoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecadienoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecadienoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecadienoyl)-2-hexadecanoyl Acyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine Choline; 1,2-bis-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-nonadecatrienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(5Z,8Z,11Z,14Z,17Z- Eicosapentaenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-henicosanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(11Z-docosadienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-tridecanoyl-glycero-3-phosphocholine;1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-pentadedecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-octadecanoyl-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-nonadecaenoyl)-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2- (5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(11Z-docoenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-pentadecanoyl-glycero-3-phosphocholine Choline; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine;1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1,2-bis-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero Oil-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1- (6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(7Z,10Z,13Z,16Z-docosetetraenoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-hexadecanoyl-glycero-3-phosphocholine; 1-nonadecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-nonadecanoyl-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-nonadecanoyl Acyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-nonadecanoyl-2-henedicosanoyl-glycero-3-phosphocholine; 1-nonadecanoyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-dodecanoyl-glycero-3-phosphocholine;1-(9Z-nonadecanoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1,2-diphosphocholine -(9Z-nonadecanoyl)-sn-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecanoyl)-2-(7Z,10Z,13Z,16Z-diicosatrienoyl)- Dodecatetraenoyl)-glycero-3-phosphocholine; 1-(9Z-nonadecaenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(9Z-pentadecaenoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-eicosanoyl-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(6Z, 9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-eicosanoyl-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-(8Z,11Z,14Z-eicosatotrienoyl)-glycero-3-phosphocholine; 1-eicosanoyl-2-heneicosanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine;1-(11Z-eicosenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl) 1-(11Z-eicosadienoyl)-2-(11Z-docosadienoyl)-glycero-3-phosphocholine; 1-(11Z-eicosadienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-tetradecanoyl-glycero-3-phosphocholine ; 1-(11Z,14Z-eicosadienoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine Choline; 1-(11Z,14Z-eicosadienoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1,2-bis-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine;1-(11Z,14Z-eicosadienoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z- 1-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2- (9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero Oil-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1,2-bis-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine;1-(8Z,11Z,14Z-eicosatrienoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(7Z,1 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; Heptadecatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl) -2-(8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-docosanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosopentaenoyl)-2-tetradecanoyl-glycero-3-phosphocholine;1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero Oil-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1,2-bis-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z- 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-pentadecanoyl-glycero-3-phosphocholine; 1-henicosanoyl-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine;1-Henicosanoyl-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-Henicosanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-Henicosanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-Henicosanoyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-Henicosanoyl-2-eicosanoyl-glycero-3-phosphocholine; 1-Henicosanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-Henicosanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero Oil-3-phosphocholine; 1-henicosanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-docosanoyl-glycero-3-phosphocholine; 1-henicosanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-henicosanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-heptadecanoyl-glycero-3-phosphocholine; 1-docosanoyl-2-( 9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-docosanoyl -2-Henicosanoyl-glycero-3-phosphocholine; 1-docosanoyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-docosanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(11Z-docosenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine;1-(11Z-docenoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(11Z-docenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(11Z-docenoyl)-2-(9Z,12Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(11Z-docenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(11Z-docenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(11Z-docenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(11Z-docenoyl)-2-(6Z,9Z ,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(11Z-docoenoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1,2-di-(11Z-docoenoyl) 1-(11Z-docosadienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(11Z-docosadienoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2- Tetradecanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-nonadecanoyl-glycero-3-phosphocholine;1-(13Z,16Z-docosadienoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(11Z-docosaenoyl)-glycero-3-phosphocholine; 1-(13Z,16Z-docosadienoyl)-2-(7Z,10Z,13Z,16Z-eicosatetraenoyl)- 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z,12Z -heptadecatetraenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)- 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-heneicosanoyl-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-docosetetraenoyl-glycero-3-phosphocholine;1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(11Z-docosatetraenoyl)-glycero-3-phosphocholine; 1,2-bis-(7Z,10Z,13Z,16Z-docosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z ,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-pentadecanoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z,12Z-heptadecadienyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-eicosanoyl-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-eicosanoyl-glycero-3-phosphocholine 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-docosanoyl-glycero-3-phosphocholine;1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-tridecanoyl-glycero-3-phosphocholine; 1-hexadecyl-2-(9Z-heptadecanoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-hexadecyl-2-heneicosanoyl- Glycerol-3-phosphocholine; 1-hexadecyl-2-(7Z,10Z,13Z,16Z-docosetetraenoyl)-glycerol-3-phosphocholine; 1-octadecyl-2-dodecanoyl-glycerol-3-phosphocholine; 1-octadecyl-2-(9Z-pentadecenoyl)-glycerol-3-phosphocholine; 1-octadecyl-2-(9Z-heptadecenoyl)-glycerol-3-phosphocholine; 1-octadecyl-2-(9Z,12Z-heptadecadienoyl)-glycerol-3-phosphocholine; 1-octadecyl-2-(9Z-octadecenoyl)-glycerol-3-phosphocholine; 1-octadecyl-2-(9Z,12Z-octadecadienoyl)-glycerol-3-phosphocholine; 1-octadecyl-2-(9Z-octadecenoyl)-glycerol-3-phosphocholine; 1-octadecyl-2-(9Z,12Z-octadecadienoyl)-glycerol-3-phosphocholine; -2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-octadecyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-octadecyl-2-heneicosanoyl-glycero-3-phosphocholine; 1-octadecyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-octadecyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-eicosyl-2-dodecanoyl-glycero-3-phosphocholine; 1-eicosyl-2-tetradecanoyl-glycero-3-phosphocholine; 1-eicosyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine Choline; 1-eicosyl-2-pentadecanoyl-glycero-3-phosphocholine; 1-eicosyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine; 1-eicosyl-2-octadecanoyl-glycero-3-phosphocholine; 1-eicosyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-eicosyl-2-nonadecanoyl-glycero-3-phosphocholine; 1-eicosyl-2-eicosanoyl-glycero-3-phosphocholine;1-eicosyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(8Z,11Z,14Z-eicosatotrienoyl)-glycero-3-phosphocholine; 1-eicosyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-dodecanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-tridecanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-pentadecanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-pentadecanoyl-glycero-3-phosphocholine )-2-hexadecanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenoyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(1Z-hexadecenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenoyl)-2-(11Z,14Z-eicosadienoyl) 1-(1Z-hexadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine; 1-(1Z-hexadecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenoyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(1Z-octadecenoyl)-2-hexadecenoyl-glycero-3-phosphocholine; 1-(1Z-octadecenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenoyl)-2-octadecanoyl-glycero-3-phosphocholine ; 1-(1Z-octadecenyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-nonadecanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine;1-(1Z-octadecenyl)-2-henicosanoyl-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-tetradecanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(9Z-pentadecenyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-hexadecanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-heptadecanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(9Z-heptadecenyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2 -(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-octadecanoyl-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(9Z-nonadecanoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenyl)-2-(5Z,8Z,11 1-(1Z-eicosenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine; 1-(1Z-eicosenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-tetradecanoyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-tetradecanoyl-2-(4Z,7Z,10Z sn-glycero-3-phosphocholine; 1-(9Z-tetradecenoyl)-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine;1-(9Z-hexadecenoyl)-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenoyl)-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine; 1-octadecanoyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(9Z ,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(13Z-docosetetraenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(7Z,10Z,13Z,16Z-docosetetraenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-eicosatetraenoyl) Tetradecanoyl-sn-glycero-3-phosphocholine; 1-(11Z-octadecenoyl)-2-(15Z-tetracoenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(13Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(9Z-octadecenoyl)-2-(15Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienoyl)-2-tetracoenoyl-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(15Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-decoecatrienoyl)-2-(15Z-docoenoyl)-sn-glycero-3-phosphocholine sn-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(13Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(15Z-eicosatrienoyl)-sn-glycero-3-phosphocholine; 1-(6Z,9Z,12Z,15Z-octadecatrienoyl)-2-(11Z-octadeceneoyl)-sn-glycero-3-phosphocholine;1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-eicosenoyl)-2-(13Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(11Z,14Z-eicosadienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-dioctadecenoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine; sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(6Z,9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 8Z,11Z-eicosatrienoyl)-2-(13Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(13Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(13Z-docoenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-(9Z,12Z-octadecadienoyl)-sn- Glycerol-3-phosphocholine; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-eicosanoyl-sn-glycerol-3-phosphocholine; 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-docosanoyl-sn-glycerol-3-phosphocholine; 1-(5Z,8Z,11Z,14Z,17Z-eicosopentaenoyl)-2-(11Z-octadecenoyl)-sn-glycerol-3-phosphocholine; 1-docosanoyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycerol-3-phosphocholine; 1-(13Z-docosanoyl)-2-tetradecanoyl-sn-glycerol-3-phosphocholine;1-(13Z-docosenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docosenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(13Z-docosenoyl)-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-(13Z-docosenoyl)-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-(13Z-docosenoyl)-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z-docosetetraenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; sn-glycero-3-phosphocholine; 1-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-2-(9Z-tetradecenoyl)-sn-glycero-3-phosphocholine; 1-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-2-(9Z-tetradecenoyl)-sn-glycero-3-phosphocholine; 1-tetracosanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-tetracosanoyl-2-(6Z,9Z,12Z,15Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(15Z-tetracosenoyl)- 2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(15Z-tetradecenoyl)-2-(6Z,9Z,12Z-octadecatetrienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenyl)-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenyl)-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-(9Z-hexadecenyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-octadecenyl -2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(11Z-octadecenyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienyl)-2-(9Z,12Z-octadecadienyl)-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienyl)-2-eicosanoyl-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienyl)-2-docosanoyl-sn-glycero-3-phosphocholine; 1-(9Z,12Z-octadecadienyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine;1-Eicosyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-Docosyl-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine; 1-Docosyl-2-(10Z,13Z,16Z-docosatrienoyl)-sn-glycero-3-phosphocholine; 1-(13Z,16Z-Eicosyl)-2-(13Z,16Z-docosatrienoyl)-sn-glycero-3-phosphocholine; 1-(13Z,16Z-Eicosyl)-2-(10Z,13Z,16Z-docosatrienoyl)-sn-glycero-3-phosphocholine; 1-Tetracosyl- 2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine; 1-tetracosyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(1Z-hexadecenyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine; 1-(1Z-octadecenyl)-2-(15Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-octadecanoyl-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine Choline; 1-(1Z,11Z-octadecadienyl)-2-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-(13Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-(13Z,16Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-tetracosadienoyl-sn-glycero-3-phosphocholine; 1-(1Z,11Z-octadecadienyl)-2-(15Z-eicosadienoyl)-sn-glycero-3-phosphocholine; 1-(1Z, sn-glycero-3-phosphocholine; 1-(1Z,9Z-octadecadienyl)-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine; 1-(1Z,9Z-octadecadienyl)-2-(13Z,16Z-docosadienoyl)-sn-glycero-3-phosphocholine; (2R)-2-hydroxy-3-[(9Z,12Z)-nonadeca-9,12-dienoyloxy]propyl 2-(trimethylammonio)ethyl phosphate; 1-(11Z-octadecadienoyl)-sn-glycero-3-phosphocholine; 1-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine;1-(13Z-docosahexaenoyl)-sn-glycero-3-phosphocholine; 1-(14Z,17Z,20Z,23Z,26Z,29Z-docosahexaenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine; 1-O-(2-methoxyhexadecyl)-sn-glycero-1-3-phosphocholine; 1-O-(2-methoxy-4Z-hexadecenyl)-sn-glycero-3-phosphocholine; 1-undecanoyl-2-hexadecanoyl -sn-glycero-3-phosphocholine; 1-hexadecyl-2-(9-carboxy-nonanoyl)-sn-glycero-3-phosphocholine; 1-(15-methyl-)hexadecyl-sn-glycero-3-phosphocholine; 1-(3Z-octadecenyl-sn-glycero-3-phosphocholine; 1-(cis-11,12-methylene-octadecanoyl)-sn-glycero-3-phosphocholine; 1-(3Z-hexadecenyl-sn-glycero-3-phosphocholine; and / or 1-(4Z-hexadecenyl-sn-glycero-3-phosphocholine.;

[0287] In some embodiments, the lipid can be a derivative of phosphatidylserine. Phosphatidylserine can be represented by formula (Ib):

[0288]

[0289] Non-limiting examples of phosphatidylserine derivatives are 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphoserine (POPS); 1,2-di-tetradecanoyl-sn-glycero-3-phosphoserine (dimyristoylphosphatidylserine or DMPS); 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoserine (dioleoylphosphatidylserine or DOPS); 1-dodecanoyl-2-tridecanoyl-sn-glycero-3-phosphoserine; 1-heptadecanoyl, 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoserine; 1-heneicosanoyl-2-(4Z, 7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphoserine; 1-heptadecanoyl-2-(9Z-tetradecenoyl)-sn-glycero-3-phosphoserine; 1-hexadecanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphoserine; 1,2-dihexanoyl-sn-glycero-3-phosphoserine; 1,2-dioctanoyl-sn-glycero-3-phosphoserine; 1,2-didecanoyl-sn-glycero-3-phosphoserine; 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoserine; 1-octadecanoyl-2-(9Z-octadecenoyl)-sn -glycerol-3-phosphoserine; 1-(9Z-octadecenoyl)-sn-glycerol-3-phosphoserine; 1-hexadecanoyl-sn-glycerol-3-phosphoserine; 1,2-di-dodecanoyl-sn-glycerol-3-phosphoserine; 1,2-di-hexadecanoyl-sn-glycerol-3-phosphoserine; 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycerol-3-phosphoserine; 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol-3-phosphoserine; 1-hexadecanoyl-2-eicosanoyl-sn-glycerol-3-phosphoserine; 1,2-di-octadecanoyl-sn-glycerol-3-phosphoserine sn-glycerophosphoryl-3-phosphoserine; 1,2-diacyl-sn-glycerophosphoryl-3-phosphoserine; 2-acyl-sn-glycerophosphoryl-3-phosphoserine; 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerophosphoryl-3-phosphoserine; 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerophosphoryl-3-phosphoserine; 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycerophosphoryl-3-phosphoserine; 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycerophosphoryl-3-phospho-N-hexadecanoyl-L-serine;1,2-Di-(9Z-octadecenoyl)-sn-glycero-3-phospho-N-nonadecanoyl-L-serine; 1-tridecanoyl-sn-glycero-3-phosphoserine; 1-octadecanoyl-sn-glycero-3-phosphoserine; 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphoserine; 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphoserine; 1-(9Z-hexadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphoserine; 1-(9Z -octadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphoserine; 1,2-bis-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphoserine; 1-dodecanoyl-glycero-3-phosphoserine; 1-tetradecanoyl-glycero-3-phosphoserine; 1-(9Z-hexadecenoyl)-glycero-3-phosphoserine; 1-(9Z,12Z-octadecadienoyl)-glycero-3-phosphoserine; 1-eicosanoyl-glycero-3-phosphoserine; 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphoserine Hexaenoyl)-glycerol-3-phosphoserine; 1-(7Z,10Z,13Z,16Z-docosetraenoyl)-glycerol-3-phosphoserine; 1-dodecanoyl-2-(9Z-tetradecenoyl)-glycerol-3-phosphoserine; 1-dodecanoyl-2-pentadecanoyl-glycerol-3-phosphoserine; 1-dodecanoyl-2-(9Z-pentadecanoyl)-glycerol-3-phosphoserine; 1-dodecanoyl-2-(9Z-hexadecenoyl)-glycerol-3-phosphoserine; 1-dodecanoyl-2-heptadecanoyl-glycerol-3-phosphoserine; 1-dodecanoyl-2-(9Z-heptadecanoyl)-glycerol-3-phosphoserine; 1-dodecanoyl-2-(9 1-Dodecanoyl-2-(9Z,12Z-octadecadienoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(9Z,12Z-octadecatrienoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-nonadecanoyl-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(9Z-nonadecanoyl)-glycerol-3-phosphoserine;1-Dodecanoyl-2-(11Z-eicosenoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(11Z,14Z-eicosadienoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycerol-3-phosphoserine; 1-Dodecanoyl-2-henicosanoyl-glycerol-3-phosphoserine; 1-Dodecanoyl -2-(11Z-docosaenoyl)-glycero-3-phosphoserine; 1-dodecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphoserine; 1-dodecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphoserine; 1-tridecanoyl-2-dodecanoyl-glycero-3...

Claims

1. A lipoprotein system, comprising: (a) apolipoprotein E (APOE); and (b) lipids; wherein said lipid is operably associated with said apolipoprotein E.

2. The lipoprotein system of claim 1, wherein the APOE comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 267-385.

3. The lipoprotein system of claim 1 or claim 2, wherein the APOE comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 267-385.

4. The lipoprotein system of any one of claims 1-3, wherein the APOE comprises an amino acid sequence of any one of SEQ ID NOs: 267-385.

5. The lipoprotein system of any one of claims 1 to 4, wherein the APOE comprises one or more mutations relative to the amino acid sequence relative to SEQ ID NO: 1 or SEQ ID NO: 268, wherein the one or more mutations are selected from the following list: A6T (SEQ ID NO: 388), A7V (SEQ ID NO: 389), L9P (SEQ ID NO: 390), V10I (SEQ ID NO: 391), T11A (SEQ ID NO: 392), T11S (SEQ ID NO: 393), F12Y (SEQ ID NO: 394), F12L (SEQ ID NO: 395), L13R (SEQ ID NO: 396), A18P (SEQ ID NO: 397), A18T (SEQ ID NO: 398), E21K (SEQ ID NO: 399), A23V (SEQ ID NO: 400), V24L (SEQ ID NO: 401), T26_E29dup (SEQ ID NO: 402), NO:402), P28L (SEQ ID NO:403), E31K (SEQ ID NO:404), R33C (SEQ ID NO:405), R33H (SEQ ID NO:406), Q35R (SEQ ID NO:407), E37K (SEQ ID NO:408), Q39R (SEQ ID NO:409), G41S (SEQ ID NO:410), R43del (SEQ ID NO:411), R43C (SEQ ID NO:412), R43H (SEQ ID NO:413), L46P (SEQ ID NO:415), L48V (SEQ ID NO:416), R50C (SEQ ID NO:417), R50S (SEQ ID NO:418), R50G (SEQ ID NO:419), R50P (SEQ ID NO:420), R50H (SEQ ID NO:421), R50L (SEQ ID NO:422), R56H (SEQ ID NO:423), T60A (SEQ ID NO:424), Q64H (SEQ ID NO:425), E68del (SEQ ID NO:426), E68V (SEQ ID NO:428), E68D (SEQ ID NO:429), L69Q (SEQ ID NO:430), L69P (SEQ ID NO:431), L70F (SEQ ID NO:432), Q73R (SEQ ID NO:433), V74A (SEQ IDNO:434)、Q76R(SEQ ID NO:435)、E77K(SEQ ID NO:436)、A80E(SEQ ID NO:437)、M82R(SEQ ID NO:438)、D83E(SEQ ID NO:439)、E84K(SEQ ID NO:440)、M86V(SEQ ID NO:441)、E88Q(SEQ IDNO:442)、L89S(SEQ ID NO:443)、K90E(SEQ ID NO:444)、K90N(SEQ ID NO:445)、Y92C(SEQID NO:446)、K93fs(SEQ ID NO:447)、K93T(SEQ ID NO:448)、K93R(SEQ ID NO:449)、K93N(SEQ ID NO:450)、S94*(SEQ ID NO:451)、Q99K(SEQ ID NO:452)、Q99R(SEQ ID NO:453)、P102R(SEQ ID NO:454)、V103L(SEQ ID NO:455)、V103L(SEQ ID NO:456)、A104T(SEQ IDNO:457)、E106Q(SEQ ID NO:458)、R108_A118dup(SEQ ID NO:459)、R108Q(SEQ ID NO:460)、R110fs(SEQ ID NO:461)、R110Q(SEQ ID NO:461)、S112Y(SEQ ID NO:462)、K113E(SEQ ID NO:463)、E114K(SEQ ID NO:464)、L115R(SEQ ID NO:465)、A117V(SEQ ID NO:466)、Q119P(SEQ ID NO:467)、A120S(SEQ ID NO:468)、A120D(SEQ ID NO:469)、R121W(SEQID NO:470)、G123R(SEQ ID NO:471)、D128N(SEQ ID NO:472)、V129M(SEQ ID NO:473)、G131C(SEQ ID NO:474)、R132C(SEQ ID NO:475)、R132L(SEQ ID NO:476)、Q135R(SEQ IDNO:477)、Y136C(SEQ ID NO:478)、R137C(SEQ ID NO:479)、R137G(SEQ ID NO:480)、R137H(SEQ IDNO:481)、G138C(SEQ ID NO:482)、V140L(SEQ ID NO:483)、V140M(SEQ ID NO:484)、L144I(SEQ ID NO:485)、G145R(SEQ ID NO:486)、G145S(SEQ ID NO:487)、G145D(SEQID NO:488)、G145A (SEQ ID NO:489)、Q146*(SEQ ID NO:490)、L151M(SEQ ID NO:491)、R152W(SEQ ID NO:492)、R152Q(SEQ ID NO:493)、V153M(SEQ ID NO:494)、R154S(SEQ IDNO:330)、R154fs(SEQ ID NO:495)、R154C(SEQ ID NO:496)、R154L(SEQ ID NO:497)、S157F(SEQ ID NO:498)、L159P(SEQ ID NO:499)、R160G(SEQ ID NO:500)、163C(SEQ ID NO:501)、R163H(SEQ ID NO:502)、K164Q(SEQ ID NO:503)、L167del(SEQ ID NO:504)、R168H(SEQ ID NO:505)、D169Y(SEQ ID NO:506)、D172N(SEQ ID NO:507)、Q174K(SEQ ID NO:508)、V179A(SEQ ID NO:509)、Y180H(SEQ ID NO:510)、Q181E(SEQ ID NO:511)、Q181H(SEQID NO:512)、A184S(SEQ ID NO:513)、G187A(SEQ ID NO:514)、G187V(SEQ ID NO:515)、G191_R198dup(SEQ ID NO:516)、E189K(SEQ ID NO:517)、R190C(SEQ ID NO:518)、G191S(SEQ ID NO:519)、S193R(SEQ ID NO:520)、R196C(SEQ ID NO:521)、R198C(SEQ ID NO:522)、G200R(SEQ ID NO:523)、R207S(SEQ ID NO:524)、R207C(SEQ ID NO:525)、R207H(SEQID NO:526)、R207P(SEQ IDNO:527)、V208L(SEQ ID NO:528)、V208M(SEQ ID NO:529)、V213G(SEQ ID NO:530)、G214S(SEQ ID NO:531)、G218R(SEQ ID NO:532)、G218S(SEQ IDNO:533)、Q219E(SEQ ID NO:534)、P220L(SEQ ID NO:535)、L221P(SEQ ID NO:536)、Q222*(SEQ ID NO:537)、Q222K(SEQ ID NO:538)、Q222R(SEQ ID NO:539)、R224P(SEQ ID NO:540)、R224L(SEQ ID NO:541)、A225T(SEQ ID NO:542)、A227S(SEQ ID NO:543)、W228*(SEQID NO:544)、G229R(SEQ ID NO:545)、G229V(SEQ ID NO:546)、E230K(SEQ ID NO:547)、R231Q(SEQ ID NO:548)、A234T(SEQ ID NO:549)、A234V(SEQ ID NO:550)、R235W(SEQ IDNO:551)、R235Q(SEQ ID NO:552)、E238del(SEQ ID NO:553)、E238D(SEQ ID NO:554)、M239I(SEQ ID NO:555)、G240R(SEQ ID NO:556)、S241R(SEQ ID NO:557)、T243fs(SEQ IDNO:558)、R242W(SEQ ID NO:559)、R242G(SEQ ID NO:560)、R242P(SEQ ID NO:561)、T243N(SEQ ID NO:562)、R246S(SEQ ID NO:563)、R246C(SEQ ID NO:564)、R246P(SEQ ID NO:565)、D248E(SEQ ID NO:566)、E249K(SEQ ID NO:567)、E249Q(SEQ ID NO:568)、E256V(SEQID NO:569)、R258H(SEQ ID NO:570)、A259P(SEQ ID NO:571)、E262K(SEQ ID NO:572)、E263K(SEQ ID NO:573)、Q267R(SEQ IDNO:574), V254E (SEQ ID NO:331), R269fs (SEQ ID NO:575), R269C (SEQ ID NO:576), R269G (SEQ ID NO:577), E273G (SEQ ID NO:578), A274G (SEQ ID NO:579), Q276* (SEQ ID NO:580), A277V (SEQ ID NO:581), R278C (SEQ ID NO:582), L279fs (SEQ ID NO:583), W282C (SEQ ID NO:584), E284G (SEQ ID NO:585), E284D (SEQ ID NO:586), L286M (SEQ ID NO:587), V287M (SEQ ID NO:588), D289A (SEQ ID NO:589), R292C (SEQ ID NO:590), R292H (SEQ ID NO:591), W294C (SEQ ID NO:592), A295T (SEQ ID NO:593), G296R (SEQ ID NO:594), G296W (SEQ ID NO:595), L297P (SEQ ID NO:596), E299Q (SEQ ID NO:597), K300R (SEQ ID NO:598), K300N (SEQ ID NO:599), V301L (SEQ ID NO:600), A303S (SEQ ID NO:601), V305M (SEQ ID NO:602), T307I (SEQ ID NO:603), A309T (SEQ ID NO:604), P311A (SEQ ID NO:605), S314R (SEQ ID NO:606), *318ext (SEQ ID NO:607), W38* (SEQ ID NO:608), E98fs (SEQ ID NO:609), A117T (SEQ ID NO:610), L122M (SEQ ID NO:611), Q141R (SEQ ID NO:612), R160C (SEQ ID NO:613), R163P (SEQ ID NO:614), K164E (SEQ ID NO:615), R165P (SEQ ID NO:616), A170P (SEQ ID NO:617), G183A (SEQ ID NO:618) and combinations thereof.

6. The lipoprotein system of claim 5, wherein the one or more mutations include R154S (SEQ ID NO.: 330).

7. The lipoprotein system of claim 5, wherein the one or more mutations include V254E (SEQ ID NO.: 331).

8. The lipoprotein system of any one of claims 1-4, wherein the APOE comprises any one of SEQ ID NOs: 275-277.

9. The lipoprotein system of any one of claims 1-8, wherein the APOE comprises one or more sequence regions selected from the group consisting of a signal sequence, an N-terminal region, a structural sequence region, a hinge region, a linker region, and a C-terminal region.

10. The lipoprotein system of claim 9, wherein the APOE comprises more than one structured sequence region.

11. The lipoprotein system of claim 10, wherein each structured sequence region is selected from an alpha helical sequence region, a beta conformation sequence region, and a beta turn sequence region.

12. The lipoprotein system of any one of claims 1-11, wherein the APOE comprises one or more chemical modifications.

13. The lipoprotein system of claim 12, wherein the one or more chemical modifications comprise one or more post-translational modifications (PTMs).

14. The lipoprotein system of claim 13, wherein the one or more post-translational modifications are selected from the following list: oxidation, carbamylation, oxidative-carbamylation, acetylation, phosphorylation, ubiquitination, biotinylation, carboxylation, deamidation, deamination, deacetylation, dihydroxylation, dephosphorylation, formylation, γ-carboxyglutamate, glutathionylation, glycation, hydroxylation, methylation, nitration, sumoylation, N- or O-transglutaminylation, glycosylation, and farnesylation.

15. The lipoprotein system of any one of claims 1-14, wherein the APOE comprises an oxidatively coupled dimer comprising two APOE monomers.

16. The lipoprotein system of claim 15, wherein the APOE monomer comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 267-385.

17. The lipoprotein system of claim 15 or claim 16, wherein the APOE monomer comprises an amino acid sequence that is at least 95% identical to any one of SEQ ID NOs: 267-385.

18. The lipoprotein system of any one of claims 15-17, wherein the APOE monomer is any one of SEQ ID NOs: 267-385.

19. The lipoprotein system of any one of claims 15-18, wherein the monomer is any one of SEQ ID NO: 268, 271, 275-277 or 294, optionally wherein the monomer is SEQ ID NO:

277.

20. The lipoprotein system of any one of claims 1 to 19, wherein the lipid comprises formula (I): in: X 1 and X 2 independently N, O or absent; R 1 and R 2 is independently optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, or absent; and R 3 Selected from:

21. The lipoprotein system of any one of claims 1 to 20, wherein the lipid is a glycerophospholipid.

22. The lipoprotein system of any one of claims 1-21, wherein the lipid is a lyso-lipid.

23. The lipoprotein system of any one of claims 1-22, wherein the lipid is phosphatidylglycerol.

24. The lipoprotein system of claim 23, wherein the phosphatidylglycerol is 1-palmitoyl-2-oleoyl-sn-glycero-3-(phospho-rac-(1-glycerol)) (POPG), 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) or 1,2-dioleoyl-sn-glycero-3-phosphoglycerol (DOPG).

25. The lipoprotein system of any one of claims 1-22, wherein the lipid is phosphatidylcholine.

26. The lipoprotein system of claim 25, wherein the phosphatidylcholine is 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or N-oleoyl-D-erythrosphingosine phosphocholine (18:1SM).

27. The lipoprotein system of any one of claims 1-22, wherein the lipid is phosphatidylserine.

28. The lipoprotein system of claim 27, wherein the phosphatidylserine is 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS), or 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS).

29. The lipoprotein system of any one of claims 1-28, wherein the lipids comprise at least 2 unique lipids.

30. The lipoprotein system of claim 29, wherein the at least two distinct lipids comprise a first lipid and a second lipid.

31. The lipoprotein system of claim 30, wherein the molar ratio of the first lipid to the second lipid is about 1:100 the first lipid: the second lipid to about 100:1 the first lipid: the second lipid.

32. The lipoprotein system of claim 30 or claim 31 , wherein the molar ratio of the first lipid to the second lipid is about 1 :1 first lipid: second lipid.

33. The lipoprotein system of any one of claims 30-32, wherein the first lipid is POPC and the second lipid is POPS.

34. The lipoprotein system of any one of claims 1-33, wherein the molar ratio of said APOE to said lipid is from about 1:10000 APOE:lipid to about 1:1 APOE:lipid.

35. The lipoprotein system of any one of claims 1-34, wherein the molar ratio of said APOE and said lipid is from about 1:500 APOE:lipid to about 1:30 APOE:lipid.

36. The lipoprotein system of any one of claims 1-35, wherein the molar ratio of said APOE and said lipid is from about 1:200 APOE:lipid to about 1:50 APOE:lipid.

37. The lipoprotein system of any one of claims 1-36, wherein the molar ratio of said APOE and said lipid is about 1:100 APOE:lipid.

38. The lipoprotein system of any one of claims 1-37, wherein the system has a disc-like, spherical, cylindrical, lamellar or ellipsoidal form.

39. The lipoprotein system of any one of claims 1 to 38, wherein the system has a disc-like form.

40. The lipoprotein system of any one of claims 1-39, wherein the diameter of the system is between 1 nm and 100 nm.

41. The lipoprotein system of any one of claims 1-40, wherein the system has a polydispersity percentage of at most 25%.

42. The lipoprotein system of any one of claims 1-41, wherein the system has a polydispersity percentage of at most 20%.

43. The lipoprotein system of any one of claims 1-42, wherein the system has a polydispersity percentage of at most 15%.

44. The lipoprotein system of any one of claims 1-43, wherein the system has a polydispersity percentage of at most 10%.

45. The lipoprotein system of any one of claims 1-44, wherein the system has a polydispersity percentage of at most 5%.

46. ​​The lipoprotein system of any one of claims 1-45, further comprising a payload.

47. The lipoprotein system of claim 46, wherein the payload is selected from the group consisting of a peptide payload, a protein payload, a nucleic acid payload, a lipid payload, a lipid derivative payload, a carbohydrate payload, a glycolipid payload, a metabolite payload, a metabolite derivative payload, and a small molecule payload.

48. The lipoprotein system of claim 46 or claim 47, wherein the payload is a small molecule payload.

49. The lipoprotein system of claim 47 or claim 48, wherein the small molecule is selected from the group consisting of antioxidants, anti-tumor agents, analgesics, anesthetics, antibacterial agents, anticonvulsants, antidementia agents, antidepressants, antiemetics, antifungals, antigout agents, anti-inflammatory agents, anti-migraine agents, anti-myasthenic agents, anti-mycobacterial agents, anti-parasitic agents, anti-Parkinson's disease agents, antipsychotic agents, anti-convulsants, anti-viral agents, antianxiety agents, bipolar disorder agents, blood glucose regulators, blood products, blood modifiers, blood volume expanders, chemotherapeutic agents, cardiovascular agents, central nervous system agents, dental oral agents, dermatological agents, electrolytes, enzyme replacement agents, enzyme modifiers, gastrointestinal agents, genitourinary system agents, immune agents, inflammatory bowel disease agents, metabolic bone disease agents, ophthalmic agents, otic agents, respiratory agents, sedatives, hypnotic agents, and skeletal muscle relaxants.

50. The lipoprotein system of claim 46 or claim 47, wherein the payload is a nucleic acid.

51. The lipoprotein system of claim 47 or claim 48, wherein the nucleic acid is RNA, DNA or cDNA.

52. The lipoprotein system of claim 51, wherein the RNA is mRNA, siRNA, microRNA, interfering RNA, replicon mRNA, RNA analog, guide RNA, or short hairpin RNA (shRNA).

53. The lipoprotein system of any one of claims 1-51, further comprising a lipoprotein system modifying agent.

54. The lipoprotein system of claim 53, wherein the lipoprotein system modifying agent is a targeting agent, a modulator, a solubilizer, a stabilizer or a detection agent.

55. A method of treating or preventing a disease or condition in a subject, the method comprising administering the lipoprotein system of any one of claims 1-54.

56. The method of claim 55, wherein the disease, injury or condition is a neurological disease, an autoimmune disease, a cardiovascular disease, a vascular disease, a respiratory disease, a metabolic disease, a gastrointestinal disease, a genetic syndrome, a cancer or a multisystem disease.

57. The method of claim 55 or claim 56, wherein the disease, injury or condition is a neurological disease.

58. The method of any one of claims 55-57, wherein the disease, injury or condition is selected from one or more of the following: degenerative cervical spondylosis, Niemann-Pick disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, Smith-Lemly-Opitz syndrome (SLOS), multiple system atrophy, prion disease, impaired cognitive function or dementia.

59. The method of claim 57 or 58, wherein the neurological disease is Niemann-Pick disease.

60. The method of claim 57 or 58, wherein the neurological disease is Alzheimer's disease.

61. The method of claim 57, wherein the neurological disease is severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection, or a neurological disease caused by SARS CoV-2 infection.

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