APOE lipoprotein system

Abstract

The present disclosure includes lipoprotein-based systems and compositions. The lipoprotein systems may optionally include a payload for delivery to a cell, tissue, organ, and / or subject in need thereof. Methods of using the lipoprotein systems are also provided herein.

Description

Technical Field

[0001] The present disclosure relates to APOE lipoproteins.

Background Art

[0002] Lipoproteins are complex molecular assemblies that play important roles in the cascades of intracellular and / or extracellular lipid metabolism. Lipids play important biological roles and function as components of cell membranes, energy reservoirs, and mediators of important signaling events. For example, brain lipids play roles in membrane formation, synaptogenesis, neurogenesis, and impulse conduction. Regulation of lipids has potential utility in the management or prevention of diseases (acute or chronic), syndromes, injuries, and / or for providing protective effects. There is a great need for compositions for regulating lipid metabolism, lipid transport, and / or effectively delivering biologically active lipids.

[0003] Effective in vivo delivery of drugs such as small molecules, proteins, peptides, nucleic acids, and other biomolecules represents an ongoing clinical challenge. Lipoproteins, by virtue of their characteristics, are excellent candidates with highly attractive properties for use as molecular transporters. The present disclosure provides a lipoprotein system that represents a highly versatile platform that can be engineered and tailored for specific applications.

Summary of the Invention

[0004] The present disclosure provides a lipoprotein system comprising apolipoproteins and lipids, such as glycerophospholipids. Apolipoproteins are known for their ability to bind to lipid molecules and to cross the blood-brain barrier. The systems of the present disclosure use this feature of apolipoproteins to design particles, such as nanoparticles, that can optionally bind to a payload, modulate lipid metabolism, and deliver the payload directly to the brain. The particles of the present disclosure can be formulated into various shapes, such as discs. The lipoprotein systems of the present disclosure can be used to treat diseases or disorders (e.g., inter alia, neurological diseases, autoimmune diseases, cardiovascular diseases, vascular diseases, respiratory diseases, metabolic diseases, gastrointestinal diseases, genetic syndromes, cancer, or multi-system diseases).

[0005] The present disclosure takes advantage of the unprecedented discovery of the biophysical advantages of a lipoprotein system comprising apolipoproteins such as apolipoprotein E (APOE) and glycerophospholipids such as phosphatidylglycerol (PG). The inclusion of glycerophospholipids such as PG lipids provides the lipoprotein systems of the present disclosure with improved polydispersity, thermal stability, and binding affinity compared to other lipoprotein systems. Further, the present disclosure provides novel peptide sequences for use in such lipoprotein systems. The novel polypeptide sequences include the assembly of each of the features of the sequences disclosed herein to generate functional polypeptide sequences for use in the present invention. The present disclosure provides lipoprotein systems of various sizes, shapes, dimensions, lipid compositions and / or apolipoprotein contents that exhibit beneficial biophysical properties.

[0006] 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, APOE comprises one or more mutations relative to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 268, and the one or more mutations are 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), 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 ID NO: 434), Q76R (SEQ ID NO: 435), E77K (SEQ ID NO: 436), A80E (SEQ ID NO: 437),M82R (Accession No. 438), D83E (Accession No. 439), E84K (Accession No. 440), M86V (Accession No. 441), E88Q (Accession No. 442), L89S (Accession No. 443), K90E (Accession No. 444), K90N (Accession No. 445), Y92C (Accession No. 446), K93fs (Accession No. 447), K93T (Accession No. 448), K93R (Accession No. 449), K93N (Accession No. 450), S94* (Accession No. 451), Q99K (Accession No. 452), Q99R (Accession No. 453), P102R (Accession No. 454), V103L (Accession No. 455), V103L (Accession No. 456), A104T (Accession No. 457), E106Q (Accession No. 458), R108_A118dup (Accession No. 459), R108Q (Accession No. 460), R110fs (Accession No. 461), R110Q (Accession No. 461), S112Y (Accession No. 462), K113E (Accession No. 463), E114K (Accession No. 464), L115R (Accession No. 465), A117V (Accession No. 466), Q119P (Accession No. 467), A120S (Accession No. 468), A120D (Accession No. 469), R121W (Accession No. 470), G123R (Accession No. 471), D128N (Accession No. 472), V129M (Accession No. 473), G131C (Accession No. 474), R132C (Accession No. 475), R132L (Accession No. 476), Q135R (Accession No. 477), Y136C (Accession No. 478), R137C (Accession No. 479), R137G (Accession No. 480), R137H (Accession No. 481), G138C (Accession No. 482), V140L (Accession No. 483), V140M (Accession No. 484), L144I (Accession No. 485), G145R (Accession No. 486), G145S (Accession No. 487), G145D (Accession No. 488), G145A (Accession No. 489), Q146* (Accession No. 490), L151M (Accession No. 491), R152W (Accession No. 492), R152Q (Accession No. 493), V153M (Accession No. 494), R154S (Accession No. 330), R154fs (Accession No. 495), R154C (Accession No. 496), R154L (Accession No. 497), S157F (Accession No. 498), L159P (Accession No. 499), R160G (Accession No. 500), 163C (Accession No. 501), R163H (Accession No. 502)K164Q (Accession No. 503), L167del (Accession No. 504), R168H (Accession No. 505), D169Y (Accession No. 506), D172N (Accession No. 507), Q174K (Accession No. 508), V179A (Accession No. 509), Y180H (Accession No. 510), Q181E (Accession No. 511), Q181H (Accession No. 512), A184S (Accession No. 513), G187A (Accession No. 514), G187V (Accession No. 515), G191_R198dup (Accession No. 516), E189K (Accession No. 517), R190C (Accession No. 518), G191S (Accession No. 519), S193R (Accession No. 520), R196C (Accession No. 521), R198C (Accession No. 522), G200R (Accession No. 523), R207S (Accession No. 524), R207C (Accession No. 525), R207H (Accession No. 526), R207P (Accession No. 527), V208L (Accession No. 528), V208M (Accession No. 529), V213G (Accession No. 530), G214S (Accession No. 531), G218R (Accession No. 532), G218S (Accession No. 533), Q219E (Accession No. 534), P220L (Accession No. 535), L221P (Accession No. 536), Q222* (Accession No. 537), Q222K (Accession No. 538), Q222R (Accession No. 539), R224P (Accession No. 540), R224L (Accession No. 541), A225T (Accession No. 542), A227S (Accession No. 543), W228* (Accession No. 544), G229R (Accession No. 545), G229V (Accession No. 546), E230K (Accession No. 547), R231Q (Accession No. 548), A234T (Accession No. 549), A234V (Accession No. 550), R235W (Accession No. 551), R235Q (Accession No. 552), E238del (Accession No. 553), E238D (Accession No. 554), M239I (Accession No. 555), G240R (Accession No. 556), S241R (Accession No. 557), T243fs (Accession No. 558), R242W (Accession No. 559), R242G (Accession No. 560), R242P (Accession No. 561), T243N (Accession No. 562), R246S (Accession No. 563), R246C (Accession No. 564), R246P (Accession No. 565), D248E (Accession No. 566), E249K (Accession No. 567)Selected from the list of 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 (SEQ ID 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), G183A (SEQ ID NO: 618), and combinations thereof. In some embodiments, one or more mutations include R154S. In some embodiments, one or more mutations include V254E. In some embodiments, APOE includes any one of SEQ ID NOs: 275-277.,

[0007] In some embodiments, APOE comprises one or more sequence regions selected from a signal sequence, an N-terminal region, a structured sequence region, a hinge region, a linker region, and a C-terminal region. In some embodiments, APOE comprises two or more structured sequence regions. In some embodiments, each structured sequence region is selected from an alpha-helical sequence region, a beta conformation sequence region, and a beta-turn sequence region.

[0008] In some embodiments, APOE comprises one or more chemical modifications. In some embodiments, the one or more chemical modifications comprise one or more post-translational modifications (PTMs). In some embodiments, the one or more post-translational modifications are selected from oxidation, carbamylation, oxycarbamylation, acetylation, phosphorylation, ubiquitination, biotinylation, carboxylation, deamidation, deamination, deacetylation, dihydroxylation, dephosphorylation, formylation, gamma-carboxyglutamidation, glutathionylation, glycylation, hydroxylation, methylation, nitration, sumoylation, N- or O-transglutamination, glycosylation, and farnesylation.

[0009] In some embodiments, APOE comprises an oxidatively linked dimer, which comprises 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.

[0010] In some embodiments, the lipid comprises formula (I),

[0011]

Chemical formula

[0012] In the formula, X 1 and X 2 are, independently, N, O, or absent, R 1 and R 2 are, independently, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, or absent, R 3 is

[0013]

Chemical formula

[0014] selected from In some embodiments, the lipid is a glycerophospholipid. In some embodiments, the lipid is a lysophospholipid.

[0015] In some embodiments, the lipid is phosphatidylglycerol. In some embodiments, 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).

[0016] In some embodiments, the lipid is phosphatidylcholine. In some embodiments, 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).

[0017] 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).

[0018] In some embodiments, the lipid comprises at least two distinct lipids. In some embodiments, the at least two distinct lipids comprise a first lipid and a second lipid. In some embodiments, the molar ratio of the first lipid to the second lipid is from about 1:100 of the first lipid to the second lipid to about 100:1 of the first lipid to the second lipid. In some embodiments, the molar ratio of the first lipid to the second lipid is about 1:1 of the first lipid to the second lipid. In some embodiments, the first lipid is POPC and the second lipid is POPS.

[0019] In some embodiments, the molar ratio of APOE to lipid is from about 1:10,000 of APOE to lipid to about 1:1 of APOE to lipid. In some embodiments, the molar ratio of APOE to lipid is from about 1:500 of APOE to lipid to about 1:30 of APOE to lipid. In some embodiments, the molar ratio of APOE to lipid is from about 1:200 of APOE to lipid to about 1:50 of APOE to lipid. In some embodiments, the molar ratio of APOE to lipid is about 1:100 of APOE to lipid.

[0020] In some embodiments, the system has a disc-like, spherical, cylindrical, sheet-like, or elliptical form. In some embodiments, the system has a disc-like form. In some embodiments, the system has a diameter of 1 nm to 100 nm. In some embodiments, the system has a polydispersity percentage of up to 25%. In some embodiments, the system has a polydispersity percentage of up to 20%. In some embodiments, the system has a polydispersity percentage of up to 15%. In some embodiments, the system has a polydispersity percentage of up to 10%. In some embodiments, the system has a polydispersity percentage of up to 5%.

[0021] 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.

[0022] In some embodiments, the payload is a small molecule payload. In some embodiments, the small molecule is selected from the group consisting of an antioxidant, an antitumor agent, an analgesic, an anesthetic, an antibacterial agent, an anticonvulsant, an anti-dementia agent, an antidepressant, an antiemetic, an antifungal agent, an antigout agent, an anti-inflammatory agent, an antimigraine agent, an anti-myasthenia agent, an antimicrobial agent, an antiparasitic agent, an anti-Parkinson agent, an antipsychotic agent, an antispasmodic agent, an antiviral agent, an antianxiety agent, a bipolar agent, a blood glucose regulator, a blood product, a blood regulator, a blood volume expander, a chemotherapeutic agent, a cardiovascular agent, a central nervous system agent, a dental oral agent, a skin agent, an electrolyte, an enzyme replacement agent, an enzyme regulator, a gastrointestinal agent, a urogenital agent, an immune agent, an inflammatory bowel disease agent, a metabolic bone disease agent, an ophthalmic agent, an otic agent, a respiratory agent, a sedative, a hypnotic, and a skeletal muscle relaxant.

[0023] 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).

[0024] In some embodiments, the nucleic acid is an antisense oligonucleoside (ASO). In some embodiments, the antisense oligonucleotide may be modified (e.g., modification at the ribose moiety of the nucleoside or at the internucleoside linkage).

[0025] In some embodiments, the lipoprotein system further comprises a lipoprotein system modifier. In some embodiments, the lipoprotein system modifier is a targeting agent, a modulator, a solubilizing agent, a stabilizing agent, or a detecting agent.

[0026] In a further aspect, the present disclosure provides a method of treating or preventing a disease or disorder in a subject, the method comprising administering a lipoprotein system as described herein. In some embodiments, the disease, injury, or disorder 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, cancer, or a multi-system disease. In some embodiments, the disease, injury, or disorder is a neurological disease. In some embodiments, the disease, injury, or disorder is selected from one or more of degenerative cervical myelopathy, Niemann-Pick disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, Smith-Lemli-Opitz syndrome (SLOS), multiple system atrophy, prion disease, cognitive impairment, or dementia. In some embodiments, the neurological disease is Niemann-Pick disease. In some embodiments, the neurological disease is Alzheimer's disease. In some embodiments, the neurological disease is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or a neurological disease caused by a SARS-CoV-2 infection.

[0027] Definitions As used herein, the terms "apolipoprotein" and its abbreviation "APO" refer to proteins that can bind to and / or interact with lipids.

[0028] As used herein, the term "apolipoprotein E" or its abbreviation "APOE" refers to any apolipoprotein E, including fragments and variants thereof. As used herein, the term "apolipoprotein variant" refers to a form or version of an apolipoprotein polypeptide or other form of apolipoprotein polypeptide or polynucleotide that differs in some respect from an apolipoprotein polypeptide or polynucleotide reference standard, or from a parental apolipoprotein polypeptide or polynucleotide, or from a starting apolipoprotein polypeptide. Such an apolipoprotein polypeptide or polynucleotide reference standard may be a parental apolipoprotein polypeptide or polynucleotide, or a starting apolipoprotein polypeptide, or a polynucleotide having a structural, sequence, or functional difference that distinguishes the apolipoprotein variant from the starting or reference standard. As used herein, an apolipoprotein variant also includes an apolipoprotein mutation that may include amino acid substitutions, deletions, insertions, and amino acid sequence modifications (e.g., reverse sequences, scrambled sequences, multi-domain sequences, switched domain sequences). As used herein, an apolipoprotein variant includes fusion polypeptides.

[0029] As used herein, the term "alpha helix sequence region" refers to a type of structure in which the polypeptide backbone is tightly wound around a hypothetical axis drawn longitudinally through the center, with the R groups of the amino acids protruding outward from the backbone. In this conformation, each backbone N-H group forms a hydrogen bond with the backbone C=O group of the amino acid located four residues ahead along the protein sequence.

[0030] As used herein, the term "beta 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 beta sheet.

[0031] As used herein, the term "beta turn sequence region" refers to a type of structure that connects the ends of two adjacent segments of a beta sheet. As used herein, the term "derivative" refers to a form or version of a compound in which at least one atom or group is different from the parent compound.

[0032] As used herein, the term "fatty acid" refers to a carboxylic acid having a long-chain hydrocarbon side group. As used herein, the term "fragment" in the context of a polypeptide refers to a continuous stretch of amino acids in the linear sequence of the polypeptide.

[0033] As used herein, the term "isolated" means that a polynucleotide, polypeptide, protein, or fragment thereof has been separated from the cells and other components with which it is normally and naturally associated. For example, with respect to a polypeptide, an isolated polypeptide is one that is separated from the amino and carboxyl termini that normally associate in its naturally occurring sequence. As will be apparent to those skilled in the art, a polynucleotide, polypeptide, protein, or fragment thereof that does not occur naturally 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 distinguishable from its naturally occurring counterpart in that its concentration or number of molecules per volume is higher ("concentrated") or lower ("separated" or "diluted") than that of its naturally occurring counterpart. A polynucleotide, polypeptide, protein, or fragment thereof need not exist in its isolated form to be distinguishable from its naturally occurring counterpart in that it differs from the naturally occurring counterpart in its primary sequence or, for example, by its glycosylation pattern, but is distinguishable from its naturally occurring counterpart by its primary sequence or, alternatively, by another characteristic such as a glycosylation pattern. Thus, a polypeptide that does not occur naturally is provided as a separate embodiment from an isolated naturally occurring polypeptide. A protein produced in a bacterial cell is provided as a separate embodiment from a naturally occurring protein isolated from the eukaryotic cell in which the protein is naturally produced.

[0034] As used herein, the term "lipoprotein system" refers to a biochemical assembly comprising one or more apolipoproteins and one or more lipids. As used herein, the term "lipoprotein system modifier" refers to any macromolecule or micromolecule that can modify / regulate the position, structure, function, solubility, detection, synthesis, assembly, and / or degradation of a lipoprotein system in vitro, ex vivo, or in vivo.

[0035] As used herein, the term "lipid" refers to a molecule of biological origin that is soluble in an organic solvent (e.g., chloroform) but shows little or no solubility in water.

[0036] As used herein, the term "nucleic acid" refers to an RNA or DNA molecule consisting of chains of ribonucleotides or deoxyribonucleotides, respectively. Further, as used herein, "nucleic acid" includes any compound or substance that comprises a polymer of nucleotides, e.g., a linked nucleoside. Such polymers may be referred to as polynucleotides.

[0037] As used herein, the term "nucleoside" refers to a molecule composed of a heterocyclic base and its sugar. As used herein, the term "nucleotide" refers to a nucleoside having a phosphate group or a variant thereof at its 3' or 5' sugar hydroxyl group. Variants of the phosphate group include, but are not limited to, saturated alkyl phosphonates, unsaturated alkenyl phosphonates, phosphorothioates, and phosphoramidites.

[0038] As used herein, the phrase "operably linked" refers to a functional connection between two or more molecules, lipids, polypeptides, entities, moieties, etc. As used herein, the term "portion" in the context of a polypeptide refers to a segment derived from a polypeptide or one or more fragments of a polypeptide.

[0039] As used herein, the term "payload" refers to any molecule associated with a lipoprotein system for delivery to a cell, tissue, subject, or biological system. The "percent sequence identity (%)" with respect to a reference polypeptide sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical to the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps if necessary to obtain the maximum percent sequence identity, without considering any conservative substitutions as part of the sequence identity. Alignments for the purpose of determining amino acid sequence identity percentages can be achieved in a variety of ways within the skill in the art, using publicly available computer software such as, for example, BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. One of ordinary skill in the art can determine appropriate parameters for aligning the sequences, including any algorithm necessary to achieve a maximum alignment over the full length of the sequences being compared.

[0040] As used herein, the term "protective mutation" is a mutation of a polypeptide or polynucleotide relative to a parental polypeptide or polynucleotide, the presence of which can prevent, protect, or shield a polynucleotide or polypeptide, or a cell, organ, system, or organism containing the polynucleotide or polypeptide, from one or more cellular fates, or diseases or disorders, such as conditions associated with neurodegeneration. By way of non-limiting example, a protective mutation can prevent or reduce the occurrence of aggregation of a polypeptide containing the protective mutation and can reduce binding to heparin, inflammation, progression of tauopathy disease, and / or neurodegeneration.

[0041] As used herein, the term "region" refers to a zone or general area. In some embodiments, when referring to a protein or polypeptide, a region may include the linear sequence of amino acids along the protein, or may include a three-dimensional area, an epitope, and / or a cluster of epitopes. 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, the terminal region may include the N-terminus and / or the C-terminus. The N-terminus refers to the end of a protein that includes an amino acid with a free amino group. The C-terminus refers to the end of a protein that includes an amino acid with a free carboxyl group. Thus, the N-terminal region and / or the C-terminal region may include the N-terminus and / or the C-terminus, as well as surrounding amino acids. In some embodiments, the N-terminal region may include any length of amino acids that includes the N-terminus but does not include the C-terminus. In some embodiments, the C-terminal region may include any length of amino acids that includes the C-terminus but does not include the N-terminus.

[0042] As used herein, the phrase "structured sequence region" refers to a region of a polypeptide that contains one or more folding patterns in its backbone formed by a stable arrangement of the amino acid residues of the polypeptide. The folding pattern may be an alpha helix, a beta conformation, or a beta turn.

[0043] As used herein, the phrase "signal sequence" refers to a sequence that can direct the transport or localization of a polypeptide. As used herein, the term "treating" refers to partially or completely reducing, ameliorating, improving, alleviating, delaying the onset, inhibiting the progression, reducing the severity, and / or reducing the occurrence of one or more symptoms or characteristics of a particular infection, disease, disorder, and / or condition. For example, "treating" cancer can refer to inhibiting the survival, growth, and / or spread of a tumor. Treatment may be administered to a subject who does not exhibit signs of a disease, disorder, and / or condition, and / or to a subject who exhibits only early signs of a disease, disorder, and / or condition, for the purpose of reducing the risk of developing the pathology associated with the disease, disorder, and / or condition.

[0044] 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 may be a parent polypeptide or polynucleotide, or an initiating polypeptide, or a polynucleotide having a structural, sequence, or functional difference that distinguishes the variant from the initiating or reference standard.

[0045] As used herein, the term "unique polypeptide" is intended to describe a polypeptide having a distinctive feature or combination of distinctive features not present in another polypeptide. Distinctive features can refer to the sequence of amino acids (natural and / or non-natural) in the polypeptide, secondary structure, post-translational modifications, chemical modifications, and / or functional characteristics.

[0046] As used herein, the term "unique lipid" is intended to describe a lipid having a distinctive feature or combination of distinctive features not present in another lipid. Distinctive features can refer to the primary structure of the lipid, the conformation of the lipid, the functional groups of the lipid, modifications to the structure of the lipid, and / or the charge of the lipid.

[0047] Details of one or more embodiments of the present disclosure are set forth in the accompanying description below. Although any materials and methods similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred materials and methods are described herein. Other features, objects, and advantages of the present disclosure will be apparent from the description. In the description, the singular forms also include the plural forms unless the context clearly dictates otherwise. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present specification will prevail.

Mode for Carrying Out the Invention

[0048] The present disclosure provides a lipoprotein system comprising apolipoproteins and lipids, such as glycerophospholipids. Apolipoproteins are known for their ability to bind to lipid molecules and to cross the blood-brain barrier. The system of the present disclosure uses this feature of apolipoproteins to design particles, such as nanoparticles, that can optionally bind to a payload, modulate lipid metabolism, and deliver the payload directly to the brain. The particles of the present disclosure can be formulated into various shapes, such as discs. The lipoprotein system of the present disclosure can be used to treat diseases or disorders (e.g., in particular, neurological diseases, autoimmune diseases, cardiovascular diseases, vascular diseases, respiratory diseases, metabolic diseases, digestive diseases, genetic syndromes, cancer, or multi-system diseases).

[0049] The present disclosure utilizes the unprecedented discovery of the biophysical advantages of lipoprotein systems that include apolipoproteins such as apolipoprotein E (APOE) and glycerophospholipids such as phosphatidylglycerol (PG). The inclusion of glycerophospholipids such as PG lipids provides the lipoprotein systems of the present disclosure with 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. The novel polypeptide sequences are generated through the assembly of the characteristics of the sequences disclosed herein to produce functional polypeptide sequences that can be formulated into lipoprotein systems. The present disclosure provides lipoprotein systems of various sizes, shapes, dimensions, lipid compositions, and / or apolipoprotein contents that exhibit beneficial biophysical properties.

[0050] The arrangement and / or positioning of the components within the system can be optimized to achieve a particular form or function. In some embodiments, the lipids may be arranged as a bilayer, while the polypeptides of the present disclosure may surround or coat the lipids. In some embodiments, one or more lipids may be present as a core surrounded by a monolayer of lipids operably associated with the polypeptides of the present disclosure. In some embodiments, the lipoprotein system may be organized into concentric spherical layers.

[0051] In some embodiments, the lipoprotein system may 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 polypeptides. In some embodiments, the lipoprotein system may 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 lipids. In some embodiments, the lipoprotein system may 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.

[0052] The lipoprotein systems of the present disclosure may be formatted into specific forms. In some embodiments, the identity of the lipids in the lipoprotein system may be modified to adjust the shape or form of the system. In some embodiments, the lipoprotein system may have a discoidal, spherical, cylindrical, lamellar, flattened or elliptical form. In preferred embodiments, the lipoprotein system has a discoidal shape.

[0053] The amounts and ratios of the lipoprotein-based components can be varied in any amount depending on the desired payload, form, function, structure, or any combination thereof. In some embodiments, the amount of each component can be expressed as a relative ratio of each component based on the number of molecules (molar ratio). In some embodiments, the lipoprotein-based system can include polypeptides and lipids in a specific molar ratio. When two or more lipids or polypeptides are present in the system, this ratio may, in some cases, reflect the ratio of combined polypeptides to lipids, or polypeptides to combined lipids, or combined polypeptides to combined lipids.Non-limiting examples of the polypeptide to lipid molar ratio 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.

[0054] In some embodiments, the polypeptide-to-lipid ratio may be designed to reflect the ratio of apolipoprotein to lipid found in naturally occurring high-density lipoprotein (HDL). In some embodiments, the lipoprotein system of the present disclosure may include one or more bilayers of lipids. In some embodiments, the lipoprotein system of the present disclosure may be a monolayer or multilayer vesicle. The monolayer vesicle can be a small unilamellar vesicle (SUV) having a diameter of about 20 to about 100 nm, a large unilamellar vesicle (LUV) having a diameter of about 100 to about 1000 nm, or a giant unilamellar vesicle (GUV) having a diameter greater than 1000 nm. In some embodiments, the multilayer vesicle (MLV) can have a diameter greater than 500 nm in which concentric bilayers form a multilayer structure. Polypeptide A polypeptide is a polymer of amino acid residues linked together, most often by peptide bonds. As used herein, the term encompasses proteins, polypeptides, or peptides of any size, structure, or function. A polypeptide can include natural, non-natural amino acids, or combinations thereof. A polypeptide can include gene products, naturally occurring polypeptides, synthetic polypeptides, homologs, orthologs, analogs, or other equivalents thereof.

[0055] The polypeptide may be a single molecule or a multimolecular complex such as a dimer, trimer, or tetramer. They may also include single-chain or multi-chain polypeptides, which may associate or link. 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 contain 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. The molecules may be derived from the same parent protein or from different parent proteins.

[0056] The polypeptides of the present disclosure may be a parent protein or may be derived from a parent protein. Any naturally occurring protein may be a parent protein of the polypeptides of the present disclosure. In some embodiments, the polypeptide variant may be derived from a parent protein or may be a variant of a parent protein. The parent protein may be a mammalian protein. In some embodiments, the parent protein may be derived from a mammal such as a human, mouse, rat, dog, pig, goat, llama, or sheep, but is not limited thereto.

[0057] In some embodiments, the polypeptides of the present disclosure may be an apolipoprotein or may be derived from an apolipoprotein. In some embodiments, the polypeptide sequences of the present disclosure can be adjusted to optimize one or more characteristics including, but not limited to, in vitro or in vivo polypeptide expression, 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 for increased in vitro or in vivo polypeptide expression, increased cholesterol efflux, increased thermal stability, increased half-life in biological fluids (e.g., cerebrospinal fluid, plasma), enhanced payload delivery, and / or improved blood-brain barrier penetration. In some embodiments, the polypeptide sequences of the present disclosure can be adjusted to decrease in vitro or in vivo expression, decrease cholesterol efflux, decrease thermal stability, decrease half-life in biological fluids (e.g., cerebrospinal fluid, plasma), delay payload delivery, and / or decrease blood-brain barrier penetration.

[0058] The polypeptides of the present disclosure can include one or more amino acids that can mimic activation sequences. For example, glutamate can function as a mimic of phosphothreonine and / or phosphoserine. Alternatively, the mimic can result in inactivation or an inactivated product containing the mimic. For example, phenylalanine can act as an inactivating substitution for tyrosine, or alanine can act as an inactivating substitution for serine.

[0059] The polypeptides of the present disclosure may include one or more post-translational modifications (PTMs). The modifications may occur in vitro, in vivo, and / or intracellularly after administration of a lipoprotein system to a subject or after administration of a polynucleotide encoding a polypeptide of the present disclosure. Post-translational modifications (PTMs) of the present disclosure include, but are not limited to, oxidation, carbamylation, oxycarbamylation, acetylation, phosphorylation, ubiquitination, biotinylation, carboxylation, deamidation, deamination, deacetylation, dihydroxylation, dephosphorylation, formylation, gamma-carboxyglutamidation, glutathionylation, glycylation, hydroxylation, methylation, nitration, sumoylation, N- or O-transglutamination, glycosylation, and farnesylation. In some embodiments, the glycosylation may be N- or O-glycosylation. In some embodiments, the glycosylation may be O-glycosylation. By way of non-limiting example, the O-glycosylation may be sialylation. The polypeptide may include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more PTMs. In some embodiments, the PTM may be present in one or more regions of the polypeptide including the structured sequence region, the N-terminal sequence region, the C-terminal sequence region, or combinations thereof.

[0060] The polypeptide can be chemically cross-linked or cyclized, either reversibly or irreversibly, by natural (e.g., disulfide bonds, native chemical ligation) or non-natural linkages (e.g., linkages resulting from "click chemistry", olefin metathesis or dimerization by a bifunctional probe). In some embodiments, the polypeptides of the present disclosure may be cross-linked, which involves chemically connecting two or more molecules by covalent bonds. The cross-linking may be within a region or portion of one polypeptide or between two or more polypeptides. Attachment between two groups on a single polypeptide results in an intramolecular cross-link that stabilizes the polypeptide tertiary or quaternary structure. Attachment between groups on two different polypeptides results in an intermolecular cross-link that stabilizes polypeptide-polypeptide interactions. Cross-linking can be achieved using homobifunctional cross-linking reagents, heterobifunctional cross-linking agents, or photoreactive cross-linking agents. Non-limiting examples of homobifunctional cross-linking agents include disuccinimidyl suberate (DSS), disuccinimidyl tartrate (DST), dithiobis(succinimidyl propionate) (DSP), bismaleimidoethane (BMOE), 1,4-bismaleimidobutane (BMB), 1,8-bismaleimido-diethylene glycol (BMB-PEG2), 1,3-dichloroacetone, or DTME. Non-limiting examples of heterobifunctional cross-linking agents include m-maleimidobenzoyl-N-hydroxysuccinimide ester (MDS), N-γ-maleimidobutyryloxy succinimide ester (GMBS), N-(ε-maleimidocaproyl oxy) succinimide ester (EMCS) or N-(ε-maleimidocaproyl oxy) sulfosuccinimide ester (sulfo-EMCS). In some embodiments, more than one type of cross-linking can be used within a given polypeptide molecule. In some embodiments, cross-linking is achieved by oxidation, reduction, UV radiation, esterification, hydrolysis, intercalating agents, neoplastic agents, formaldehyde, formalin, silica compounds, siloxane cross-linking, or photocross-linking. In some embodiments, linkers such as small organic molecules (esters, amines) or inorganic molecules (silica, siloxane), including those of its microparticles or nanoparticles, can be used to cross-link multiple molecules.

[0061] The polypeptides of the present disclosure may, in some cases, consist of multiple polypeptide chains that come together to form dimers, trimers, tetramers, pentamers, hexamers, heptamers, oligomers (polypeptide chains less than 50) or multimers (polypeptide chains more than 50) by covalent bonds or non-covalent forces. Each of such proteins may have multiple N-termini and C-termini. Alternatively, the termini of the polypeptide may, in some cases, be modified to begin or end with a non-polypeptide-based moiety such as an organic conjugate.

[0062] In some embodiments, the lipoproteins or polypeptides of the present disclosure may be modified to reduce their immunogenicity. Immunogenicity is the result of a series of responses to substances perceived as foreign and may include the production of neutralizing and non-neutralizing antibodies, the formation of immune complexes, complement activation, mast cell activation, inflammation, hypersensitivity responses, and anaphylaxis. Several factors, including but not limited to protein sequence, route and frequency of administration, and patient population, can contribute to protein immunogenicity. Protein engineering may be used to reduce the immunogenicity of the compositions of the present disclosure. Modifications for reducing immunogenicity may include those 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 may be modified such that there are substantially zero or minimal numbers of immune epitopes present in the compositions of the present disclosure that are predicted to bind to any common MHC allele. Several methods for identifying MHC-binding epitopes of known protein sequences are known in the art and may be used to score the epitopes in the compositions of the present disclosure. Such methods are disclosed in U.S. Patent Publications Nos. US20020119492, US20040230380, and US20060148009, the contents of each of which are incorporated by reference in their entirety.

[0063] Epitope identification and subsequent sequence modifications may be applied to reduce immunogenicity. Identification of immunogenic epitopes can be achieved physically or computationally. Physical methods of epitope identification can include, for example, mass spectrometry and tissue culture / cell techniques. To identify peptides that may result from antigen processing, information related to antigen processing, loading and presentation, structure and / or proteomics data can be utilized, and computational approaches that are likely to have good binding properties to the MHC groove can also be utilized. One or more mutations can be introduced into the polypeptides of the present disclosure to make the identified epitopes less immunogenic or non-immunogenic while maintaining functionality.

[0064] In some embodiments, protein modifications to the structure of the compositions of the present disclosure for interfering with antigen processing and peptide loading, such as glycosylation and PEGylation, may also be useful in the present disclosure. The compositions of the present disclosure may also include non-classical amino acid side chains. Any of the methods discussed in International Patent Publication WO2005051975 for reducing immunogenicity may be useful in the present disclosure (the contents of which are incorporated by reference in their entirety).

[0065] In some embodiments, the polypeptides of the present disclosure may include modified amino acids or amino acid derivatives. As used herein, the terms “modified amino acid” or “amino acid derivative” refer to non-proteinogenic amino acids, i.e., amino acids that are not one of the 20 common amino acids. In some embodiments, the modified amino acids or amino acid derivatives are formed by post-translational modifications. In some embodiments, the modified amino acids or amino acid derivatives are formed by artificial synthetic processes. In some embodiments, the modified amino acids or amino acid derivatives include side chain substituents that are substituted by another substituent. In some embodiments, the modified amino acids or amino acid derivatives include protecting groups or other substituents attached to functional groups such as amino groups or carboxyl groups. Exemplary modifications include, but are not limited to, carboxylation, hydroxylation, acylation, alkylation, amidation, acetylation, lipidation, lipoylation, hypusination, prenylation, glipyatyon, phosphopantetheinylation, retinylidene Schiff base formation, diphthamide formation, amide bond formation, butyrylation, γ-carboxylation, glycosylation, polysialylation, iodination, nucleotide addition, phosphate ester or phosphoramidate formation, phosphorylation, adenylylation, uridylylation, propionylation, pyroglutamate formation, S-glutathionylation, S-nitrosylation, S-sulfenylation, S-sulfinylation, S-sulfonylation, succinylation, glycation, carbamylation, carbonylation, biotinylation, oxidation, pegylation, ISGylation, SUMOylation, ubiquitination, neddylation, pupylation, citrullination, deimination, deamidation, eliminylation, and disulfide bridging. Apolipoproteins and apolipoprotein variants In some embodiments, the polypeptide of the present disclosure may comprise or be derived from a parent polypeptide such as an apolipoprotein. As used herein, "apolipoprotein" can be used to refer to a protein that can bind to and / or interact with lipids. The binding or interaction between an apolipoprotein and a lipid may be direct or indirect.

[0066] An apolipoprotein can be in a prepro form (also referred to herein as a preprotein form), a mature form, or a processed form. For example, when an apolipoprotein is first expressed in endothelial vesicles as a preproprotein or prepro form. The preprotein form may include a signal sequence that can be removed after being transported across the Golgi apparatus to its target location, such as the extracellular space. This form may be referred to herein as the "mature form." Thereafter, a portion of the amino acid sequence can be cleaved by the action of an intracellular or extracellular proteolytic cleavage enzyme that generates the processed form of the apolipoprotein.

[0067] 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.

[0068] In some embodiments, the apolipoprotein may be a human apolipoprotein. In some embodiments, the apolipoprotein may be a non-human apolipoprotein. Non-limiting examples of non-human species include monkeys, chimpanzees, rats, mice, horses, sheep, cats, dogs, cows, or rabbits. Apolipoprotein variant In some embodiments, the apolipoprotein may differ from other forms of apolipoprotein in some respects (i.e., is a variant of another apolipoprotein). Such an apolipoprotein may be a parent apolipoprotein or starting apolipoprotein polypeptide, or a polynucleotide having a structural, sequence, or functional difference that distinguishes the apolipoprotein variant from a starting standard or reference standard.

[0069] 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 variants of any known apolipoprotein.

[0070] Generally, an apolipoprotein variant can have at least about 70%, at least 80%, or at least 90% identity with other forms of the protein. The percentage identity as used herein is defined as the number of residues (amino acids or nucleic acids) that are identical to a second amino acid or nucleic acid sequence per 100 residues of the first sequence, after aligning the sequences and introducing gaps as necessary to achieve the maximum percentage identity. The final value of the percentage identity can be affected by the gaps and penalties introduced into the calculation to achieve the maximum value. The percentage identity of an apolipoprotein can be calculated for the entire apolipoprotein or only for a region or portion thereof. In some embodiments, the percentage 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 percentage identity can be at least 60% - 70%, 65% - 75%, 70% - 80%, 75% - 85%, 85% - 95%, 90 - 99%, or 95 - 99.99%. The percentage identity of a polypeptide to a known apolipoprotein can be 10% - 20%, 10% - 25%, 10% - 50%, 10% - 60%, 10% - 70%, 10% - 80%, 10% - 90%, 10% - 95%, 20% - 25%, 20% - 50%, 20% - 60%, 20% - 70%, 20% - 80%, 20% - 90%, 20% - 95%, 20% - 99%, 50% - 60%, 50% - 70%, 50% - 80%, 50% - 90%, 50% - 95%, 50% - 99%, 70% - 80%, 70% - 90%, 70% - 95%, 70% - 99%, 80% - 90%, 80% - 95%, 80% - 99%, 90% - 95%, 90% - 99%, and 95% - 99%, but less than 100%.Percent identity to a particular reference polynucleotide or polypeptide can be determined by an alignment program, 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 terms “identical” or percent “identity” refer to amino acid residues or nucleotides having a particular percentage (e.g., 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) that are the same or that are aligned and compared for maximum correspondence over a comparison window or designated region using a sequence comparison algorithm or by manual alignment and visual inspection. Such sequences that are at least about 80% identical are said to be “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 (e.g., the shorter of two sequences having different lengths). In various embodiments, identity can refer to the complement of the test sequence.

[0071] In some embodiments, the identity is present over a region that is at least about 2 to about 400 amino acids or nucleotides in length. In some embodiments, the identity is present 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 is present 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, at least about 2 to about 5 amino acids or nucleotides in length. In some embodiments, the identity is present over a region that is 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, 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, about 35 to about 400 amino acids or nucleotides in length.In some embodiments, the identity is present over a region that is 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 to 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 length. In some embodiments, the identity is present over a region that is 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 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, about 25 to about 62 amino acids or nucleotides in length.

[0072] In some embodiments, the apolipoprotein variant may be a substitution variant of another apolipoprotein. As used herein, the term "substitution variant" when referring to a polypeptide means that at least one amino acid residue of the native or starting sequence has been removed and a different amino acid has been inserted in its place at the same position. The substitution may be single, where only one amino acid in the molecule is substituted, or multiple, where two or more amino acids in the same molecule are substituted. In some embodiments, the apolipoprotein may include conservative amino acid substitutions. As used herein, the term "conservative amino acid substitution" refers to the substitution of an amino acid normally present in the sequence with a different amino acid of similar size, charge, or polarity. Examples of conservative substitutions include the substitution of one nonpolar (hydrophobic) residue, such as isoleucine, valine, and leucine, with another nonpolar residue. Similarly, examples of conservative substitutions include the substitution of one polar (hydrophilic) residue, such as between arginine and lysine, between glutamine and asparagine, and between glycine and serine, with another polar (hydrophilic) residue. Further, the substitution of one basic residue, such as lysine, arginine, or histidine, with another basic residue, or the substitution of one acidic residue, such as aspartic acid or glutamic acid, with another acidic residue, are additional examples of conservative substitutions. In some embodiments, the apolipoprotein variant may include non-conservative substitutions. Examples of non-conservative substitutions include the substitution of a nonpolar (hydrophobic) amino acid residue, such as isoleucine, valine, leucine, alanine, methionine, etc., with a polar (hydrophilic) residue, such as cysteine, glutamine, glutamic acid, or lysine, and / or the substitution of a polar residue with a nonpolar residue.

[0073] In some embodiments, the apolipoprotein variant may be an insertion variant. As used herein, the term "insertion variant," when referring to a polypeptide, has one or more amino acids inserted immediately adjacent to an amino acid at a specific position in the native or starting sequence. As used herein, the term "immediately adjacent" refers to an adjacent amino acid that is connected to either the alpha-carboxy or alpha-amino functional group of the starting amino acid or reference amino acid.

[0074] In some embodiments, the apolipoprotein variant may be a deletion variant. As used herein, the term "deletion variant," when referring to a polypeptide, has one or more amino acids removed from the native or starting amino acid sequence. Generally, a deletion variant has one or more amino acids deleted in a specific region of the polypeptide.

[0075] The systems of the present disclosure may also include peptides that mimic the structure and / or activity of apolipoproteins. By way of non-limiting example, the present disclosure may include any of the agonists described in US6,004,925, US6,037,323, US6,046,166, U.S. 5,840,688, the entire contents of each of which are incorporated herein by reference.

[0076] In some embodiments, the apolipoprotein may be derived from a non-human apolipoprotein or may be a variant of a non-human apolipoprotein. Non-human species can include monkeys, chimpanzees, rats, mice, horses, sheep, cats, dogs, cows, and / or rabbits.

[0077] The apolipoproteins or apolipoprotein variants of the present disclosure can have N-terminal or C-terminal truncations, or can have one or more internal deletions or insertions with respect to other forms of apolipoprotein polypeptides. The apolipoproteins used in the methods and compositions of the present disclosure can be multimers of an apolipoprotein or a part thereof, for example, two or more copies of an apolipoprotein or its variant or part thereof linked by a linker. The apolipoproteins used in the methods and compositions of the present disclosure can be chimeric apolipoproteins that include the sequences of two different apolipoproteins (or their variants). Furthermore, the apolipoprotein can be bound to a peptide or another protein sequence, for example, as part of a fusion protein. The peptide sequence can be, for example, a purification and / or detection tag.

[0078] Non-limiting examples of apolipoproteins are shown in Table 1.

[0079]

Table 1

[0080] In some embodiments, the apolipoprotein is a variant or mutant of the proteins in Table 1. APOE The polypeptides of the present disclosure can be apolipoprotein E (APOE) or derivatives and / or variants derived from APOE. This protein family binds to lipids and interacts with the low-density lipoprotein receptor (LDLR), which is important in the processing of triglyceride-rich proteins. In peripheral tissues, APOE can be 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, which are members of the LDLR family.

[0081] APOE is widely distributed across lipoprotein classes and is present in chylomicron remnants, mature very low-density lipoproteins (VLDL), VLDL remnants, low-density lipoproteins (LDL), and high-density lipoproteins (HDL). It binds with high affinity to the LDL receptor and the LRP receptor family. APOE promotes the clearance of chylomicrons and VLDL remnants. Approximately 60% of plasma APOE is present in HDL, and HDL exchanges it with other lipoproteins. APOE is synthesized by hepatocytes, macrophages, and brain astrocytes. APOE, together with APOA, controls cholesterol efflux from cells. It also has antioxidant properties and plays a role in the regulation of the inflammatory response. Different variants of APOE can have different affinities for lipids, lipoproteins, and receptors, and the selection of the APOE variant included in the lipoprotein system of the present disclosure can be adjusted accordingly.

[0082] The 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 modifications (e.g., reverse sequences, scrambled sequences, multi-domain sequences, switched domain sequences).

[0083] In some embodiments, the APOE variant may 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.

[0084] In some embodiments, the apolipoprotein may be the region of amino acids (aa) 18 - 317 of another apolipoprotein, e.g., APOE3 (SEQ ID NO: 268), aa18 - 317 of APOE2 (SEQ ID NO: 267), aa18 - 317 of APOE4 (SEQ ID NO: 269).

[0085] In some embodiments, the polypeptides of the present disclosure can be APOE variants associated with a disease or disorder. In some embodiments, the polypeptides of the present disclosure can be APOE variants associated with diseases such as, but not limited to, neurological disorders (e.g., Alzheimer's disease), cardiovascular diseases (e.g., hyperlipoproteinemia, familial dysbetalipoproteinemia, hypercholesterolemia, familial combined hyperlipidemia), or kidney diseases (e.g., lipoprotein glomerulopathy). APOE variants have been identified as major genetic modifiers of Alzheimer's disease (AD) that contribute to the susceptibility of late-onset AD. APOE affects amyloid production, aggregation, and clearance, is a component of amyloid plaques, and exacerbates tau-mediated neurodegeneration. APOE2 confers some protection 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 entire 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 develop hyperlipoproteinemia type III (HLP III), while other APOE variants are linked to autosomal dominant HLP III. HLP III is characterized by increased plasma cholesterol and triglyceride levels, as well as the presence of tuberous or linear palmar xanthomas. In some embodiments, the polypeptides of the present disclosure may be APOE variants associated with cognitive decline in aging. Individuals with the APOE-ε4 allele showed memory decline before the age of 60 and a greater acceleration than non-carriers (Caselli et al., N Engl J Med. 2009;361:255-63).

[0086] 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 includes serine at position 154 of the APOE protein sequence (SEQ ID NOs: 1-3). As used herein, APOE Christchurch can also be referred to as APOE(R136S) or APOE of SEQ ID NOs: 268, 267, 269, which includes amino acids (aa) 18-317 of SEQ ID NOs: 1-3. In some embodiments, the APOE Christchurch variant may 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 may 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 was supported by in vitro experiments demonstrating that the APOE Christchurch variant can behave like APOE2, but 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 each of which are incorporated herein by reference in their entirety). These findings suggest that the AD-related chain of pathogenic events is likely disrupted by APOE3ChC after amyloid formation, and that the Christchurch mutation is protective, independent of its mechanism.

[0087] In some embodiments, the APOE variant can be the APOE Jacksonville variant (also referred to herein as APOE Jac). As used herein, the term APOE Jacksonville variant can be used to refer to an APOE protein sequence that includes glutamic acid at position 254 (V254E) of the APOE protein sequence (SEQ ID NOs: 1-3). APOE Jacksonville as used herein can also be referred to as APOE(V236E) with respect to APOE of SEQ ID NO: 268, 267, or 269, which includes amino acids (aa) 18-317 of SEQ ID NOs: 1-3. In some embodiments, the APOE Jacksonville variant can be the APOE3 Jacksonville 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. 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 content of which is incorporated herein by reference in its entirety).

[0088] The APOE variants of the present disclosure can include one or more mutations at positions discussed herein with respect to APOE3 (SEQ ID NO: 1), APOE2 (SEQ ID NO: 2), and APOE4 (SEQ ID NO: 3).

[0089] In some embodiments, the APOE protein can be a variant of human APOE3 (SEQ ID NO: 1, reference ensemble PRT ID ENSP00000252486). Mutations to APOE3 are 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), 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 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 ID NO: 442), L89S (SEQ ID NO: 443), K90E (SEQ ID NO: 444), K90N (SEQ ID NO: 445), Y92C (SEQ ID 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 (Accession No. 454), V103L (Accession No. 455), V103L (Accession No. 456), A104T (Accession No. 457), E106Q (Accession No. 458), R108_A118dup (Accession No. 459), R108Q (Accession No. 460), R110fs (Accession No. 461), R110Q (Accession No. 461), S112Y (Accession No. 462), K113E (Accession No. 463), E114K (Accession No. 464), L115R (Accession No. 465), A117V (Accession No. 466), Q119P (Accession No. 467), A120S (Accession No. 468), A120D (Accession No. 469), R121W (Accession No. 470), G123R (Accession No. 471), D128N (Accession No. 472), V129M (Accession No. 473), G131C (Accession No. 474), R132C (Accession No. 475), R132L (Accession No. 476), Q135R (Accession No. 477), Y136C (Accession No. 478), R137C (Accession No. 479), R137G (Accession No. 480), R137H (Accession No. 481), G138C (Accession No. 482), V140L (Accession No. 483), V140M (Accession No. 484), L144I (Accession No. 485), G145R (Accession No. 486), G145S (Accession No. 487), G145D (Accession No. 488), G145A (Accession No. 489), Q146* (Accession No. 490), L151M (Accession No. 491), R152W (Accession No. 492), R152Q (Accession No. 493), V153M (Accession No. 494), R154S (Accession No. 330), R154fs (Accession No. 495), R154C (Accession No. 496), R154L (Accession No. 497), S157F (Accession No. 498), L159P (Accession No. 499), R160G (Accession No. 500), 163C (Accession No. 501), R163H (Accession No. 502), K164Q (Accession No. 503), L167del (Accession No. 504), R168H (Accession No. 505), D169Y (Accession No. 506), D172N (Accession No. 507), Q174K (Accession No. 508), V179A (Accession No. 509), Y180H (Accession No. 510), Q181E (Accession No. 511), Q181H (Accession No. 512), A184S (Accession No. 513), G187A (Accession No. 514), G187V (Accession No. 515), G191_R198dup (Accession No. 516)E189K (Accession No. 517), R190C (Accession No. 518), G191S (Accession No. 519), S193R (Accession No. 520), R196C (Accession No. 521), R198C (Accession No. 522), G200R (Accession No. 523), R207S (Accession No. 524), R207C (Accession No. 525), R207H (Accession No. 526), R207P (Accession No. 527), V208L (Accession No. 528), V208M (Accession No. 529), V213G (Accession No. 530), G214S (Accession No. 531), G218R (Accession No. 532), G218S (Accession No. 533), Q219E (Accession No. 534), P220L (Accession No. 535), L221P (Accession No. 536), Q222* (Accession No. 537), Q222K (Accession No. 538), Q222R (Accession No. 539), R224P (Accession No. 540), R224L (Accession No. 541), A225T (Accession No. 542), A227S (Accession No. 543), W228* (Accession No. 544), G229R (Accession No. 545), G229V (Accession No. 546), E230K (Accession No. 547), R231Q (Accession No. 548), A234T (Accession No. 549), A234V (Accession No. 550), R235W (Accession No. 551), R235Q (Accession No. 552), E238del (Accession No. 553), E238D (Accession No. 554), M239I (Accession No. 555), G240R (Accession No. 556), S241R (Accession No. 557), T243fs (Accession No. 558), R242W (Accession No. 559), R242G (Accession No. 560), R242P (Accession No. 561), T243N (Accession No. 562), R246S (Accession No. 563), R246C (Accession No. 564), R246P (Accession No. 565), D248E (Accession No. 566), E249K (Accession No. 567), E249Q (Accession No. 568), E256V (Accession No. 569), R258H (Accession No. 570), A259P (Accession No. 571), E262K (Accession No. 572), E263K (Accession No. 573), Q267R (Accession No. 574), V254E (Accession No. 331), R269fs (Accession No. 575), R269C (Accession No. 576), R269G (Accession No. 577), E273G (Accession No. 578), A274G (Accession No. 579), Q276* (Accession No. 580), A277V (Accession No. 581)It includes R278C (Accession No. 582), L279fs (Accession No. 583), W282C (Accession No. 584), E284G (Accession No. 585), E284D (Accession No. 586), L286M (Accession No. 587), V287M (Accession No. 588), D289A (Accession No. 589), R292C (Accession No. 590), R292H (Accession No. 591), W294C (Accession No. 592), A295T (Accession No. 593), G296R (Accession No. 594), G296W (Accession No. 595), L297P (Accession No. 596), E299Q (Accession No. 597), K300R (Accession No. 598), K300N (Accession No. 599), V301L (Accession No. 600), A303S (Accession No. 601), V305M (Accession No. 602), T307I (Accession No. 603), A309T (Accession No. 604), P311A (Accession No. 605), S314R (Accession No. 606), *318ext (Accession No. 607), W38* (Accession No. 608), E98fs (Accession No. 609), A117T (Accession No. 610), L122M (Accession No. 611), Q141R (Accession No. 612), R160C (Accession No. 613), R163P (Accession No. 614), K164E (Accession No. 615), R165P (Accession No. 616), A170P (Accession No. 617), and G183A (Accession No. 618). In some embodiments, the APOE protein may be a variant of APOE3 (Accession Nos. 1-3). Exemplary mutations include S2I (Accession No. 619), G4E (Accession No. 620), A5T (Accession No. 621), S6F (Accession No. 622), R7K (Accession No. 623), P12S (Accession No. 624), N14K (Accession No. 625), P17S (Accession No. 626), P18L (Accession No. 627), D19N (Accession No. 628), W20C (Accession No. 629), I22fs (Accession No. 630), T23K (Accession No. 631), G24D (Accession No. 632), G24V (Accession No. 633), and K26fs (Accession No. 634) (see Accession Nos. 619-634).

[0090] In some embodiments, the APOE protein may be a variant of SEQ ID NO: 5. Exemplary mutations include S2I (Accession No. 619), G4E (Accession No. 620), A5T (Accession No. 621), S6F (Accession No. 622), R7K (Accession No. 623), P12S (Accession No. 624), N14K (Accession No. 625), P17S (Accession No. 626), P18L (Accession No. 627), D19N (Accession No. 628), W20C (Accession No. 629), I22fs (Accession No. 630), T23K (Accession No. 631), G24D (Accession No. 632), G24V (Accession No. 633), and K26fs (Accession No. 634) (see Accession Nos. 619-634).

[0091] APOA In some embodiments, the polypeptides of the present disclosure may comprise or be derived from APOA. In some embodiments, APOA can be APOA1 (also referred to herein as apolipoprotein A-I, Apo A-I, 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 A-V, Apo A-V, ApoA-V, Apo A5, ApoA5).

[0092] In some embodiments, the polypeptides of the present disclosure comprise or are derived from APOA1 or a variant thereof. APOA1 is a 243 - amino acid protein. The APOA gene is located on chromosome 11 and is part of the APOA1 / C3 / A4 / A5 gene cluster. It is synthesized in the liver and the intestine. The concentration of APOA1 is controlled by its degradation rate. APOA1 constitutes 70% of the HDL apolipoprotein. It activates LCAT and is also an anti - inflammatory molecule and an antioxidant. Plasma levels of APOA1 vary depending on the measurement method and the population.

[0093] In some embodiments, the polypeptides of the present disclosure 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 mainly expressed in the liver. APOA2 accounts for about 20% of the HDL protein. HDL particles contain either only APOA1 or both APOA1 and APOA2. The APOA2 concentration is determined by its production rate. It inhibits LPL activity (and may also inhibit HTGL) and functions as a co - factor for LCAT and CETP.

[0094] In some embodiments, the polypeptide of the present disclosure comprises or is 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. Since it is relatively hydrophilic, it can be replaced from lipoproteins by APOE and circulates mainly as a lipid-free protein. It is involved in intestinal lipid absorption, chylomicron assembly, and affects various aspects of the lipoprotein response to diet.

[0095] In some embodiments, the polypeptide of the present disclosure comprises or is derived from APOA5 or a variant thereof. APOA5 regulates the synthesis and secretion of hepatic VLDL. The gene encoding APOA5 is strongly associated with triglyceride (TG) concentration. APOA5 deficiency results in type V dyslipidemia and a decrease in post-heparin LPL activity. On the other hand, its overexpression results in a decrease in TG concentration. APOA5 is synthesized in the liver.

[0096] In some embodiments, the APOA variant may include the mutations R175C (referred to herein as APOA Paris or APOA1 Paris) and / or R197C (referred to herein as APOA Milano or APOA1 Milano) with respect to ENSP00000236850 (SEQ ID NO: 9).

[0097] The APOA variants of the present disclosure may include one or more mutations at the positions discussed herein with respect to REF ENSMBL PRT ID ENSP00000236850. Mutations to AOPA1 are 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), 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 (SEQ ID NO: 675), E193K (SEQ ID NO: 676), D192E (SEQ ID NO: 677), D192N (SEQ ID NO: 678), Y190C (SEQ ID NO: 679), P189R (SEQ ID NO: 680), A188G (SEQ ID NO: 681), A188V (SEQ ID NO: 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 (SEQ ID NO: 693), E171K (SEQ ID NO: 694),E170K (Accession No. 695), E170* (Accession No. 696), L168P (Accession No. 697), L168V (Accession No. 698), S166R (Accession No. 699), L165R (Accession No. 700), K164N (Accession No. 701), E163G (Accession No. 702), E163K (Accession No. 703), Q162P (Accession No. 704), E160D (Accession No. 705), E160K (Accession No. 706), E160Q (Accession No. 707), H159Q (Accession No. 708), Q156R (Accession No. 709), R155L (Accession No. 710), A154V (Accession No. 711), A154T (Accession No. 712), E152K (Accession No. 713), Q151* (Accession No. 714), L150I (Accession No. 715), R147H (Accession No. 716), E144K (Accession No. 717), K142R (Accession No. 718), R140C (Accession No. 719), R140S (Accession No. 720), Y139* (Accession No. 721), Y139H (Accession No. 722), M136T (Accession No. 723), E134A (Accession No. 724), Q133E (Accession No. 725), W132C (Accession No. 726), W132L (Accession No. 727), K131del (Accession No. 728), K131M (Accession No. 729), K130R (Accession No. 730), Q129P (Accession No. 731), D127N (Accession No. 732), D126G (Accession No. 733), Y124* (Accession No. 734), P123S (Accession No. 735), P123T (Accession No. 736), V121A (Accession No. 737), A119V (Accession No. 738), D113E (Accession No. 739), M110I (Accession No. 740), R107S (Accession No. 741), E104D (Accession No. 742), E104K (Accession No. 743), K101E (Accession No. 744), E100G (Accession No. 745), L99P (Accession No. 746), D97N (Accession No. 747), F95Y (Accession No. 748), T92I (Accession No. 749), L88F (Accession No. 750), Q87H (Accession No. 751), K83N (Accession No. 752), F81Y (Accession No. 753), F81I (Accession No. 754), T78I (Accession No. 755), L71del (Accession No. 756), L71V (Accession No. 757), N67K (Accession No. 758), L66L (Accession No. 759), G63fs (Accession No. 760), L62F (Accession No. 761)It contains 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 ID NO: 772), D44E (SEQ ID NO: 773), V43L (SEQ ID 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).

[0098] The APOA variants of the present disclosure may contain one or more mutations at the positions discussed herein with respect to REF ENSMBL PRT ID ENSP00000364478. Mutations with respect 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), 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), A218P (SEQ ID NO: 820), R212G (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), F21del (SEQ ID NO: 831), S22P (SEQ ID NO: 832), F21L (SEQ ID NO: 833), F21S (SEQ ID NO: 834), F20L (SEQ ID NO: 835), H15L (SEQ ID NO: 837), P14S (SEQ ID NO: 838), G7S (SEQ ID NO: 839), R6Q (SEQ ID NO: 840), R6W (SEQ ID NO: 841), G4R (SEQ ID NO: 842), G3A (SEQ ID NO: 843), G3R (SEQ ID NO: 844), or M1I (SEQ ID NO: 845).

[0099] Characteristics of the polypeptide In some embodiments, the polypeptides of the present disclosure may include one or more components or features. As used herein, the term "feature", when referring to a protein or polypeptide, is defined as a component based on the different amino acid sequences of the molecule. In some embodiments, the polypeptides of the present disclosure may include at least one structured sequence region. In some embodiments, the polypeptides of the present disclosure may include from about 2 to about 30 structured sequence regions, such as from about 5 to about 25 structured sequence regions, from about 10 to about 20 structured sequence regions, about 15 structured sequence regions, and the like. In some embodiments, the polypeptides of the present disclosure may further include a signal sequence, an N-terminal sequence region, a C-terminal sequence region, or a hinge region, a linker region, or a combination thereof.

[0100] The features of the polypeptides of the present disclosure include surface expression, local three-dimensional conformational shape, folding, loops, half-loops, domains, half-domains, sites, termini, or any combination thereof. In some embodiments, the polypeptides of the present disclosure include one or more surface expressions. As used herein, the term "surface expression", when referring to a protein, refers to the polypeptide-based component of the protein that appears on the outermost surface.

[0101] In some embodiments, the polypeptides of the present disclosure include one or more local three-dimensional conformational shapes. As used herein, the term "local three-dimensional conformational shape", when referring to a protein, refers to the structural expression of the polypeptide of the protein that is located within a definable space of the protein.

[0102] In some embodiments, the polypeptides of the present disclosure include one or more folds. As used herein, the term "fold" when referring to a protein refers to the resulting three-dimensional structure of the amino acid sequence upon energy minimization. Folding can occur at the secondary or tertiary level of the folding process. Examples of secondary level folds include beta sheets and alpha helices. Examples of tertiary folds include domains and regions formed by the aggregation or separation of energy forces. The regions thus formed include hydrophobic and hydrophilic pockets, among others.

[0103] In some embodiments, the polypeptides of the present disclosure include one or more turns. As used herein, the term "turn" in relation to a protein structure refers to a bend that changes the direction of the peptide or polypeptide backbone and can include one, two, three, or more amino acid residues.

[0104] In some embodiments, the polypeptides of the present disclosure include one or more loops. As used herein, the term "loop" when referring to a protein refers to a structural feature of a peptide or polypeptide that reverses the direction of the peptide or polypeptide backbone and includes four or more amino acid residues. Oliva et al. have identified at least five classes 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 content of which is incorporated herein by reference in its entirety).

[0105] In some embodiments, the polypeptides of the present disclosure include one or more half-loops. As used herein, the term "half-loop," when referring to a protein, refers to a portion of a specified loop that has at least half the number of amino acid residues as the loop from which it is derived. It should be understood that loops may not necessarily contain an even number of amino acid residues. Thus, when a loop contains or is specified to contain an odd number of amino acids, the half-loop of the odd loop includes the integer part or the next integer part of the loop (number of amino acids in the loop / 2 + / - 0.5 amino acids). For example, a loop specified as a 7-amino acid loop can generate a 3-amino acid or 4-amino acid half-loop (7 / 2 = 3.5 + / - 0.5 is 3 or 4).

[0106] In some embodiments, the polypeptides of the present disclosure include one or more motifs and / or domains. A motif is a short sequence (less than 40 residues) pattern associated with one or more distinguishable structural or functional features or properties (e.g., binding ability, functioning as a site for protein-protein interaction). In some embodiments, a motif refers to a distinct structural site that performs a specific function. A domain is also a conserved sequence pattern defined as an independent functional and structural unit. Domains are typically longer than motifs. Domains consist of more than 40 residues and up to 700 residues, with an average length of 100 residues. A domain may or may not contain a motif within its boundaries.

[0107] In some embodiments, the polypeptides of the present disclosure include one or more half-domains. As used herein, the term "half-domain," when referring to a protein, refers to a portion of a specified domain that has at least half the number of amino acid residues as the domain from which it is derived. It should be understood that a domain may not necessarily contain an even number of amino acid residues. Thus, when a domain is determined to contain an odd number of amino acids, the half-domains of the odd domain include the integer portion or the next integer portion of the domain (number of amino acids in the domain / 2 + / - 0.5 amino acids). For example, a domain specified as a 7-amino acid domain can generate a 3-amino acid or 4-amino acid half-domain (7 / 2 = 3.5 + / - 0.5 is 3 or 4). Sub-domains can be specified within a domain or half-domain, and it is also understood that these sub-domains have fewer characteristics than all of the structural or functional characteristics specified within the domain or half-domain from which they are derived. It is also understood that amino acids containing any of the domain types herein need not be contiguous along the polypeptide backbone (i.e., non-adjacent amino acids can be structurally folded to form a domain, half-domain, or sub-domain).

[0108] In some embodiments, the polypeptides of the present disclosure include one or more sites. As used herein, the term "site" with respect to amino acid-based embodiments is used synonymously with "amino acid residue" and "amino acid side chain." A site represents a position within a peptide or polypeptide that can be modified, manipulated, altered, derivatized, or changed within the polypeptide-based molecule of the present disclosure.

[0109] Polypeptide features can be manipulated and / or modified by movement, exchange, inversion, deletion, randomization, or duplication. It should be understood that further, manipulation of the features can result in the same outcome as modification of the compositions of the present disclosure. For example, manipulation involving deletion of a domain will result in a change in the length of the molecule, similar to modification of a nucleic acid encoding less than the full-length molecule. Modification and manipulation can be accomplished by methods known in the art such as site-directed mutagenesis. The resulting modified molecules can then be tested for activity using in vitro or in vivo assays such as those described herein, or any other suitable screening assay known in the art.

[0110] In some embodiments, the polypeptides of the present disclosure may be modified to modulate polypeptide binding to lipids and / or receptors. Modifications may be introduced into the polypeptide to alter or modulate 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 disclosure may be modified to alter one or more properties including, but not limited to, aggregation, complement binding, half-life, and / or stability.

[0111] 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 within a parent protein or polypeptide that interacts with a receptor, such as an apolipoprotein. The interaction between the domain and the receptor can result in cells containing the receptor to perform a specific function and / or acquire a specific phenotype. In some embodiments, the polypeptide of the present disclosure may include the 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), LDL receptor-related protein (LRP, such as LRP1, LRP4, LRP8), very low density lipoprotein receptor (VLDLR), scavenger receptor class B member (SCARB1), apolipoprotein B receptor (APOBR), nuclear receptor subfamily 1 group H member 2 (NR1H2), and / or nuclear receptor subfamily 2 group F member 2 (NR2F2). In some embodiments, the receptor-binding domain may include the region starting from 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, 180 to amino acid 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 of APOE3 (SEQ ID NO: 1), APOE2 (SEQ ID NO: 2) or APOE4 (SEQ ID NO: 3), or variants thereof. Non-limiting examples of receptor-binding domains may include regions such as aa130-150, 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 for modulating receptor-binding properties. The polypeptides of the present disclosure may also include one or more mutations for modulating accessibility to the receptor-binding sequence. In some embodiments, the compositions of the present disclosure may include point mutations within a binding region that increase receptor and matrix binding. In some embodiments, the compositions of the present disclosure may include point mutations within a binding region that decrease receptor and matrix binding. In some embodiments, the compositions of the present disclosure may include point mutations within a binding region that independently modulate receptor binding and matrix binding. For example, in some embodiments, the compositions of the present disclosure may include point mutations within a binding region that increase receptor binding and decrease matrix binding.

[0112] In some embodiments, the polypeptides of the present disclosure may include mutations that affect the tendency of the polypeptide to aggregate. The 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).

[0113] In some embodiments, the polypeptides of the present disclosure may include one or more heparin-binding and / or heparan sulfate proteoglycan-binding regions. The heparin-binding region may be derived from a parent protein, such as, but not limited to, an apolipoprotein, such as APOE. The heparin-binding region in APOE may include residues in the vicinity of 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 content of which is incorporated herein by reference in its entirety).

[0114] In some embodiments, the polypeptides of the present disclosure may include one or more glycosylation sites, which as used herein refers to sites within the polypeptides of the present disclosure that may be enzymatically modified to include a carbohydrate moiety. In some embodiments, the apolipoprotein variant may include one or more mutations that increase the 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 include one or more mutations for reducing the 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 such that alanine prevents its glycosylation.

[0115] In some embodiments, the polypeptides of the present disclosure further include 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 added to a protein, such 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 is removable by chemical agents or by enzymatic means such as proteolysis or intein splicing.

[0116] Structured sequence region In some embodiments, the polypeptides of the present disclosure may include one or more structured sequence regions. As used herein, "structured sequence region" refers to a region of a polypeptide that contains one or more folding patterns in its backbone, formed by a stable arrangement of amino acid residues of the polypeptide. The folding pattern may be an alpha helix, a beta conformation, a beta turn, or a combination thereof. In some embodiments, the structured sequence region of the 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, the polypeptide includes structured sequence regions derived from multiple (e.g., combinations) of parent proteins.

[0117] The structured sequence region (SSR) may be an alpha helix sequence region or may include an alpha helix sequence region. As used herein, an alpha helix sequence refers to a type of structure in which the polypeptide backbone is tightly wound around a hypothetical axis that is drawn longitudinally through the center, and the R groups of the amino acids project outward from the backbone. In this conformation, each backbone N-H group forms a hydrogen bond with the backbone C=O group of the amino acid located four residues ahead along the protein sequence.

[0118] In some embodiments, the alpha helix array region may be one or more amphipathic alpha helix array regions or may include one or more amphipathic alpha helix array regions. An amphipathic (or amphiphilic) helix is used to refer to an α-helix and may include both hydrophobic and hydrophilic amino acid residues arranged to form two faces on opposite sides of the helix, with one face being hydrophobic and the other face being hydrophilic. In some embodiments, the amino acid sequence of the amphipathic helix may include hydrophilic amino acids every second or third position of the sequence. The amphipathic alpha helices described herein may also include amino acids having hydrophobic side chains every third or fourth position.

[0119] In some embodiments, the SSR may include a helix bundle. As used herein, the term "helix bundle" refers to a protein fold composed of several alpha helices that may be parallel to each other, or nearly parallel, or antiparallel.

[0120] The SSRs of the present disclosure may include one or more peptides. The SSR peptides may be of any length, for example, about 2 to 55 amino acids long. In some embodiments, the peptides within the SSR may be 11 amino acids (referred to herein as "11-mers") or multiples thereof, such as, but not limited to, 22-mers, 33-mers, 44-mers, or 55-mers. In some embodiments, the SSR peptide may be, or may be a part of, an amphipathic alpha-helical sequence region. In some embodiments, the polypeptides of the present disclosure may include about 5 to about 30 SSR peptides. The SSR peptides (SSRP) may be derived from the same parent protein, or the polypeptides of the present disclosure may include SSR peptides derived from two or more parent proteins. In some embodiments, one or more of the SSRPs may be repeated in the polypeptides of the present disclosure. In some embodiments, point mutations are introduced that affect the tendency to aggregate, glycosylation, receptor binding, or other properties. In some embodiments, a linker region may be introduced between lipid-binding alpha helices.

[0121] In some embodiments, the SSRP does not occur naturally. In some embodiments, the SSRP may include a hydrophobic surface that engages with lipids and a polar surface that engages with charged residues that promote electrostatic interactions between the solubility in an aqueous medium and within 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 than or longer than 11 residues.

[0122] Table 2 shows non-limiting examples of SSRP sequences.

[0123]

Table 2-1

[0124]

Table 2-2

[0125] The polypeptides of the present disclosure can include a plurality of amphiphilic α-helices covalently linked using well-established fragment conjugation or ligation chemistries described in the comprehensive review “Synthesis of Native Proteins by Chemical Ligation” 2000, Ann Rev Biochem 69:923-60, the contents of which are hereby incorporated by reference in their entirety. In some embodiments, ligation of helices and linker segments can be performed as described in “Synthesis of Native Proteins by Chemical Ligation” 2000, Ann Rev Biochem 69:923-60. The α-helices can be separated by short linker sequences that can be provided by sequences of natural or non-natural amino acids. In some embodiments, the linker sequence can form an amino acid loop.

[0126] In some embodiments, the SSR may be a beta conformation array region or may include a beta structure array region. As used herein, "beta conformation array region" refers to a type of structure in which the backbone of the polypeptide 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 beta sheet. The zigzag polypeptide chains can be arranged side by side to form a structure similar to a series of pleats. Hydrogen bonds are formed between adjacent segments of the polypeptide chain. The individual segments that form the beta sheet are usually close to the polypeptide chain but can also be very far apart from each other in the linear sequence of the polypeptide, and they can be segments of different polypeptide chains. In some embodiments, adjacent polypeptide chains within the beta sheet can be either parallel or antiparallel (having the same or opposite amino-carboxyl orientation, respectively). The beta sheet domain can be fundamental in establishing strong binding of the lipoproteins of the present disclosure to lipids. In some embodiments, one or more amphipathic alpha helix domains may be located between two beta sheet domains.

[0127] In some embodiments, the SSR may be a beta turn array region or may include a beta turn array region. As used herein, "beta turn array region" refers to a type of structure that connects the ends of two adjacent segments of a beta sheet.

[0128] In some embodiments, the structured array region of the present disclosure can include one or more folding patterns, or variants thereof, having a configuration such as ABABAB or AABBAABBAABB or ABCABCABC that is repeated more than once, twice, or three times. In these patterns, each letter, A, B, or C, represents a different folding pattern. In yet another embodiment, the polypeptide of the present disclosure may include two or more folding pattern component arrays, each component having one or more arrays. By way of non-limiting example, the arrays can be patterns such as ABABAB or AABBAABBAABB or ABCABCABC, or variants thereof, that are repeated more than once, twice, or three times in each region of the region.

[0129] In some embodiments, the SSR can include one or more gap arrays adjacent to the folding pattern present therein. The gap array can connect adjacent folding patterns within the SSR.

[0130] 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 array 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, 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, 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-mers).

[0131] In some embodiments, the structured array region contains hydrophobic residues on its inner surface. In some embodiments, the hydrophobic residues on the inner surface of the structured array region bind to lipid acyl chains. In some embodiments, the structured array region contains endogenous hydrophobic residues on its inner surface. In some embodiments, the structured array region includes substitution of any amino acid with a hydrophobic amino acid so as to have hydrophobic residues on its inner surface. In some embodiments, the structured array region includes substitution of any amino acid with a hydrophobic amino acid so as to increase the hydrophobic residues on its inner surface. In some embodiments, the structured array region includes substitution of any hydrophilic or neutral amino acid with a hydrophobic amino acid so as to have hydrophobic residues on its inner surface. In some embodiments, the structured array region includes substitution of any hydrophilic or neutral amino acid with a hydrophobic amino acid so as to increase the hydrophobic residues on its inner surface.

[0132] In some embodiments, the structured array region contains hydrophilic residues on its outer surface. In some embodiments, the hydrophilic residues on the outer surface of the structured array region solubilize the lipoprotein particles in an aqueous medium or solution.

[0133] In some embodiments, the structured array region contains endogenous hydrophilic residues on its outer surface. In some embodiments, the structured array region includes substitution of any amino acid with a hydrophilic amino acid so as to have hydrophilic residues on its outer surface. In some embodiments, the structured array region includes substitution of any amino acid with a hydrophilic amino acid so as to increase the hydrophilic residues on its outer surface. In some embodiments, the structured array region includes substitution of any hydrophobic or neutral amino acid with a hydrophilic amino acid so as to have hydrophilic residues on its outer surface. In some embodiments, the structured array region includes substitution of any hydrophobic or neutral amino acid with a hydrophilic amino acid so as to increase the hydrophilic residues on its outer surface.

[0134] In some embodiments, the structured array region contains 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 array region is an intramolecular interaction. In some embodiments, the interaction between the top or bottom surfaces of adjacent peptides in the structured array region is an intermolecular interaction.

[0135] In some embodiments, the structured array region contains endogenous high-charge residues on its top or bottom surface. In some embodiments, the structured array region contains endogenous, for example, Arg or Glu residues on its top or bottom surface. In some embodiments, the structured array region includes substitution of any amino acid with a high-charge amino acid such that it has high-charge residues on its top or bottom surface. In some embodiments, the structured array region includes substitution of any amino acid with a high-charge amino acid such that it increases the high-charge residues on its top or bottom surface. In some embodiments, the structured array region includes substitution of any neutral amino acid with a high-charge amino acid such that it has high-charge residues on its top or bottom surface. In some embodiments, the structured array region includes substitution of any neutral amino acid with a high-charge amino acid such that it increases the hydrophilic residues on its outer surface.

[0136] In some embodiments, the structured array region includes substitution of any amino acid, for example with Arg or Glu, such that it has high-charge residues on its top or bottom surface. In some embodiments, the structured array region includes substitution of any amino acid, for example with Arg or Glu, such that it increases the high-charge residues on its top or bottom surface. In some embodiments, the structured array region includes substitution of any neutral amino acid, for example with Arg or Glu, such that it has high-charge residues on its top or bottom surface. In some embodiments, the structured array region includes substitution of any neutral amino acid, for example with Arg or Glu, such that it increases the hydrophilic residues on its outer surface.

[0137] In some embodiments, the residues on the upper or lower surface of the structured array region are substituted with a plurality of natural or non-natural amino acids. In some embodiments, the residues on the upper or lower surface of the structured array region are substituted with one natural or non-natural amino acid. In some embodiments, the residues on the upper or lower surface of the structured array region are substituted with Cys or Tyr. In some embodiments, the substituted residues on the upper or lower surface of the structured array region crosslink a plurality of molecules via covalent or non-covalent bonds. In some embodiments, the covalent bond is a disulfide bond. In some embodiments, the structured array region provides a structural component for lipid binding. In some embodiments, the structured array region binds to an ATP-binding cassette transporter (ABC transporter) and stimulates cholesterol efflux. In some embodiments, the structured array region functions as a site for chemical crosslinking. In some embodiments, the polypeptides of the present disclosure form dimers. In some embodiments, the polypeptide forms a homodimer. In some embodiments, the polypeptide forms a disulfide homodimer. In some embodiments, the polypeptide forms a dimer by utilizing a protein dimerizing agent. As used herein, the term "protein dimerizing agent," also known as a chemical inducer of dimerization, refers to a compound that binds to two different proteins and brings them into proximity only in the presence of the dimerizing agent. Protein dimerizing agents are commonly used to construct protein complexes.Exemplary protein dimerizers include 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 the FKBP and FRB (FKBP-rapamycin binding) domains of mTOR dimers, coumermycin for GyrB (DNA gyrase subunit B) homodimers, gibberellin for GAI (a member of the DELLA protein) and GID1 (gibberellin-insensitive dwarf1) 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, but are not limited thereto. In some embodiments, the non-natural means include photoinduced dimerization. Exemplary photoinduced dimerization includes, but is not limited to, the use of photosensitive proteins or photocaged chemical dimers.

[0138] In some embodiments, the first or last residue in the SSRP is a helix-breaking residue, thereby allowing flexibility between consecutive helices. In some embodiments, the helix-breaking residue is Pro or Gly. In some embodiments, the SSRP stimulates ABCA (ATP-binding cassette transporter A) / ABCG (ATP-binding cassette transporter G)-mediated cholesterol efflux. In some embodiments, the SSRP may be sufficient to stimulate ABCA / ABCG-mediated cholesterol efflux.

[0139] In some embodiments, the SSRP may be derived from the alignment of apolipoprotein consensus repeat units. In some embodiments, the apolipoprotein consensus repeat units may be combined in a non-natural order. In some embodiments, the apolipoprotein consensus repeat units may be derived from the sequence of non-human APOE. In some embodiments, the apolipoprotein consensus repeat units may be derived from the sequence of other exchangeable apolipoproteins (e.g., ApoA1 or ApoA-1). In some embodiments, the apolipoprotein consensus repeat units may be derived from the sequence of ApoA1 or ApoA-1.

[0140] In some embodiments, the structured sequence region may include point mutations or chemical crosslinks to modify the accessibility and effective affinity of the binding region. In some embodiments, the structured sequence region may include point mutations that introduce additional Arg residues to modify the protein's aggregation tendency, protease stability, and its half-life in the endosome / lysosome compartment. In some embodiments, the structured sequence region may include point mutations to modify the multimerization tendency of the polypeptide in solution.

[0141] N-terminal sequence region In some embodiments, the polypeptide of the present disclosure may include an N-terminal sequence region. The N-terminal sequence region may be derived from any parent protein or polypeptide. In some aspects, the N-terminal sequence region is derived from an apolipoprotein (referred to herein as the "apolipoprotein N-terminal sequence region"). As a non-limiting example, the apolipoprotein may be APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, or APOO. In some embodiments, the N-terminal sequence region may include a region or fragment of the terminal region of the parent protein or polypeptide. In some embodiments, the N-terminal sequence region may include a region or fragment of the N-terminus of the parent protein or polypeptide (terminated by an amino acid having a free amino group (NH2)). In some embodiments, the N-terminal region may include any length of amino acids that includes the N-terminus but does not include the C-terminus of the parent protein or polypeptide.For example, the N-terminal sequence region may include 1 to 10, 5 to 15, 10 to 20, 15 to 25, 20 to 30, 25 to 35, 30 to 40, 35 to 45, 40 to 50, 45 to 55, 50 to 60, 55 to 65, 60 to 70, 65 to 75, 70 to 80, 75 to 85, 80 to 90, 85 to 95, 90 to 100, 95 to 105, 100 to 110, 105 to 115, 110 to 120, 115 to 125, 120 to 130, 125 to 135, 130 to 140, 135 to 145, 140 to 150, 145 to 155, 150 to 160, 155 to 165, 160 to 170, 165 to 175, 170 to 180, 175 to 185, 180 to 190, 185 to 195, 190 to 200, 195 to 205, 200 to 210, 205 to 215, 210 to 220, 215 to 225, 220 to 230, 225 to 235, 230 to 240, 235 to 245, 240 to 250, 245 to 255, 250 to 260, 255 to 265, 260 to 270, 265 to 275, 270 to 280, 275 to 285, 280 to 290, 285 to 295, 290 to 300, 295 to 305, 300 to 310, 305 to 315, 310 to 320, 315 to 325, 320 to 330, 325 to 335, 330 to 340, 335 to 345, 340 to 350, 345 to 355, 350 to 360, 355 to 365, 360 to 370, 365 to 375, 370 to 380, 375 to 385, 380 to 390, 385 to 395, 390 to 400, 400 to 500, 500 to 1000, 1000 to 5000 from the N-terminus of any parent protein or polypeptide.

[0142] In some embodiments, the N-terminal sequence region may be an APOE N-terminal sequence region or an APOA1 N-terminal sequence region. Table 3 shows N-terminal sequence regions of non-limiting examples. The N-terminal sequence region may contain additional amino acids or fewer amino acids compared to any of the amino acids listed in Table 3. Such amino acid sequences may contain about one or more or fewer amino acids, about two or more or fewer amino acids, about three or more or fewer amino acids, about four or more or fewer amino acids, about five or more or fewer amino acids, about six or more or fewer amino acids, about seven or more or fewer amino acids, about eight or more or fewer amino acids, about nine or more or fewer amino acids, about ten or more or fewer amino acids, or more or fewer amino acids exceeding ten.

[0143]

Table 3

[0144] C-terminal sequence region In some embodiments, the 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 an apolipoprotein. As a non-limiting example, the apolipoprotein may be APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, or APOO (referred to herein as the "apolipoprotein C-terminal sequence region"). In some embodiments, the C-terminal sequence region may include a region or fragment of the terminal region of the parent protein or polypeptide. In some embodiments, the C-terminal sequence region may include a region or fragment of the C-terminus (terminated by an amino acid having a carboxy group (NH2)) of the parent protein or polypeptide. In some embodiments, the C-terminal region may include any length of amino acids that includes the C-terminus but does not include the N-terminus of the parent protein or polypeptide.For example, the C-terminal sequence region may include 1 to 10, 5 to 15, 10 to 20, 15 to 25, 20 to 30, 25 to 35, 30 to 40, 35 to 45, 40 to 50, 45 to 55, 50 to 60, 55 to 65, 60 to 70, 65 to 75, 70 to 80, 75 to 85, 80 to 90, 85 to 95, 90 to 100, 95 to 105, 100 to 110, 105 to 115, 110 to 120, 115 to 125, 120 to 130, 125 to 135, 130 to 140, 135 to 145, 140 to 150, 145 to 155, 150 to 160, 155 to 165, 160 to 170, 165 to 175, 170 to 180, 175 to 185, 180 to 190, 185 to 195, 190 to 200, 195 to 205, 200 to 210, 205 to 215, 210 to 220, 215 to 225, 220 to 230, 225 to 235, 230 to 240, 235 to 245, 240 to 250, 245 to 255, 250 to 260, 255 to 265, 260 to 270, 265 to 275, 270 to 280, 275 to 285, 280 to 290, 285 to 295, 290 to 300, 295 to 305, 300 to 310, 305 to 315, 310 to 320, 315 to 325, 320 to 330, 325 to 335, 330 to 340, 335 to 345, 340 to 350, 345 to 355, 350 to 360, 355 to 365, 360 to 370, 365 to 375, 370 to 380, 375 to 385, 380 to 390, 385 to 395, 390 to 400, 400 to 500, 500 to 1000, 1000 to 5000 residues from the C-terminus of any parent protein or polypeptide.

[0145] In some embodiments, the C-terminal sequence region may be an APOE C-terminal sequence region or an APOA1 C-terminal sequence region. Table 4 provides exemplary C-terminal sequence regions. The C-terminal sequence region may be any of these sequences in Table 4, or may contain additional or fewer amino acids compared to those listed. Such amino acid sequences may contain about 1 more or fewer amino acids, about 2 more or fewer amino acids, about 3 more or fewer amino acids, about 4 more or fewer amino acids, about 5 more or fewer amino acids, about 6 more or fewer amino acids, about 7 more or fewer amino acids, about 8 more or fewer amino acids, about 9 more or fewer amino acids, about 10 more or fewer amino acids, or more or fewer amino acids exceeding 10.

[0146]

Table 4

[0147] Linker In some embodiments, the lipoprotein system of the present disclosure may include a linker. As used herein, the term "linker" refers to any molecule or group of molecules that connects two molecules or two portions of a molecule, such as two regions of a polypeptide. In some embodiments, the linker is a peptidyl linker. In some embodiments, the peptidyl linker comprises a short peptide of 1 to about 25 amino acids. In some embodiments, the peptidyl linker comprises 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 linker comprises glycine and serine. In some embodiments, the residues of the peptidyl linker are glycine or serine. In some embodiments, the residues of the peptidyl linker are glycine and serine. In some embodiments, the peptidyl linker may be rich in glycine for flexibility and serine or threonine for solubility.

[0148] 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 comprises a chemical reactive functional group for reacting with a second chemical reactive functional group, thereby forming a covalent linker. In some embodiments, the chemical linker comprises a linker obtained by reacting two reactive groups (moieties), such as covalent reactive groups (e.g., alkyne, thiol, azide, maleimide). In some embodiments, the chemical linker is polyvalent and / or formed by conjugate chemistry techniques. Examples of chemical linkers include, but are not limited to, -O-, -S-, -C(O)-, -C(O)O-, -C(O)NH-, -S(O)2NH-, -NH-, -NHC(O)NH-.

[0149] In some embodiments, the linker comprises a linear structure. In some embodiments, the linker comprises a non-linear structure. In some embodiments, the linker comprises a branched structure. In some embodiments, the linker comprises a cyclic structure.

[0150] In some embodiments, the linker conjugates or links a plurality of polypeptides, or fragments of polypeptides or compounds. In some embodiments, the linker binds to two polypeptides or compounds. In some embodiments, the linker binds to three polypeptides or compounds.

[0151] In some embodiments, the "linker" (L) or "linker domain" or "linker region" or "linker module" or "peptide linker" as used herein refers to an oligo- or polypeptide region of about 1 to 100 amino acids in length that covalently links together any of the domains / regions of a polypeptide (also referred to as a peptide linker). The peptide linker may be 1 to 40 amino acids in length, or 2 to 30 amino acids in length, or 20 to 80 amino acids in length, or 50 to 100 amino acids in length. The linker length can be optimized according to the type of polypeptide or payload being utilized and based on the crystal structure of the polypeptide or payload. In some cases, a shorter linker length may be preferably selected. In some aspects, the peptide linker is composed of amino acids covalently linked by peptide bonds, preferably 1 to 20 amino acids linked by peptide bonds, and the amino acids are selected from the 20 natural amino acids of 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), aspartate (D), glutamate (E), asparagine (N), and glutamine (Q). One or more of these amino acids may be glycosylated, as will be understood by those skilled in the art. 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).

[0152] In one embodiment, the artificially designed peptide linker may 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. Longer linkers can be used when it is desirable to ensure that two adjacent domains do not interfere with each other. The selection of a particular linker sequence may depend on whether it affects the biological activity, stability, folding, targeting, and / or pharmacokinetic characteristics of the fusion construct.

[0153] The linker sequence may be a natural linker derived from a multi-domain protein. A natural linker is a short peptide sequence that separates two different domains or motifs within a protein. For example, the linker sequence may be a hinge sequence derived from apolipoprotein or a variant thereof. Table 5 shows non-limiting examples of linkers useful in the present disclosure.

[0154] [Table 5-1]

[0155] [Table 5-2]

[0156] [Table 5-3]

[0157] [Table 5-4]

[0158] [Table 5-5]

[0159] Hinge In some embodiments, the polypeptides of the present disclosure may include one or more hinge regions. As used herein, a hinge connects two molecules or two portions of a molecule, such as two regions of a polypeptide, and is a molecule that promotes conformational or structural flexibility by allowing each of the two molecules or portions to move relative to the other and includes one or more amino acids. In some embodiments, the hinge region may mediate the dynamics of lipid binding by providing an opening of the helix necessary to initiate lipid binding. In some embodiments, the hinge region sequence is mutated to modify the proteolytic stability of the polypeptides of the present disclosure. The hinge can be located within a structured sequence region, an N-terminal sequence region, a C-terminal sequence region, or between an N-terminal sequence region and a structured sequence region, or between a structured sequence region and a C-terminal sequence region, or between any other region or fragment of the polypeptides of the present disclosure. The hinge region can be any suitable sequence derived from or obtained from any suitable molecule. The hinge sequence can be derived from all or part of an apolipoprotein. In some embodiments, the polypeptides of the present disclosure may not include a hinge region. Table 6 shows non-limiting examples of hinge sequences.

[0160]

Table 6-1

[0161]

Table 6-2

[0162]

Table 6-3

[0163]

Table 6-4

[0164]

Table 6-5

[0165]

Table 6-6

[0166]

Table 6-7

[0167]

Table 6-8

[0168] Signal sequence The polypeptides of the present disclosure may further include one or more additional features such as one or more signal sequences.

[0169] A signal sequence (sometimes referred to as a signal peptide, targeting signal, target peptide, localization sequence, transport peptide, leader sequence or leader peptide) directs proteins or polypeptides to their designated cellular and / or extracellular locations. Protein signal sequences play a central role in the targeting and translocation of almost all secreted proteins and many integral membrane proteins. In some embodiments, the signal sequence may direct the polypeptides of the present disclosure towards secretion.

[0170] A signal sequence is a short (5-30 amino acids in length) peptide that is present at the N-terminus of most newly synthesized proteins directed to a particular location. Signal sequences are recognized by the signal recognition particle (SRP) and can be cleaved using type I and type II signal peptidases. In some embodiments, the signal sequence may, but does not necessarily, be located at the N-terminus or C-terminus of the polypeptide and may, but does not necessarily, be cleaved from the polypeptides of the present disclosure.

[0171] In some embodiments, the signal peptide according to the present disclosure is located at the N-terminus of the protein of interest or at the N-terminus of the proprotein form of the protein of interest. The signal peptide according to the present disclosure can be of eukaryotic origin, such as the signal peptide of a eukaryotic protein, such as of mammalian origin, such as the signal peptide of a mammalian protein, more preferably of human origin, such as the signal peptide of a mammalian protein.

[0172] In some embodiments, the signal sequence can be derived from an apolipoprotein. Non-limiting examples of apolipoprotein signal sequences are shown in Table 7. All signal sequence parent apolipoproteins in Table 7 are derived from human apolipoproteins.

[0173]

Table 7

[0174] In addition to signal sequences that occur naturally, such as from secreted proteins, the signal sequence can be a variant modified from a known signal sequence of a protein. For example, U.S. Pat. Nos. 8,258,102 and 9,133,265 to Sleep disclose modified albumin signal sequences having additional X1-X2-X3-X4-X5-motifs that can increase secretion signals and protein secretion, U.S. Pat. No. 9,279,007 to Do discloses a signal sequence of a modified fragment of human immunoglobulin heavy chain binding protein (Bip) that can improve protein expression and secretion, and U.S. Pat. No. 8,148,494 to Leonhartsberger et al. discloses a signal peptide having a cleavage site that can be fused to a recombinant protein, the contents of each of which are incorporated by reference in their entirety.

[0175] The signal sequence can be selected based on their compatibility with the secretory pathway of the target cell type such that the payload is presented on the surface of T cells. Other signal sequence variants that can be used for this polypeptide may include those discussed in US Patent Application Publication No. 2007 / 0141666 and PCT Patent Application Publication No. 1993 / 018181, the entire contents of each of which are hereby incorporated by reference in their entirety.

[0176] 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 location such as the nucleus (e.g., EP1209450). Other examples include the aspartic protease (NSP24) signal sequence from Trichoderma (e.g., US Patent No. 8,093,016 to Cervin and Kim) that can increase the secretion of fusion proteins such as enzymes, the bacterial lipoprotein signal sequence (e.g., PCT Application Publication No. 1991 / 09952 to Lau and Rioux), the E. coli enterotoxin II signal peptide (e.g., US Patent No. 6,605,697 to Kwon et al.), the E. coli secretion signal sequence (e.g., US Patent Publication No. 2016 / 090404 to Malley et al.), the lipase signal sequence from methylotrophic yeast (e.g., US Patent No. 8,975,041), and the signal peptide of DNase from Coryneform bacteria (e.g., US Patent No. 4,965,197), the entire contents of each of which are hereby incorporated by reference in their entirety.

[0177] Fusion polypeptide In some embodiments, the polypeptides of the disclosure can be fusion polypeptides. As used herein, the term "fusion polypeptide" can typically refer to a single continuous peptide molecule containing two or more parent proteins or regions or portions thereof encoded by different genes. The fusion polypeptide can have functional properties derived from each of the original proteins.

[0178] The components of the fusion polypeptide can be arranged from the amino terminus to the carboxy terminus of a continuous region of the fusion protein. The regions may be directly linked to each other or may be linked via a linker. Protein linkers assist in the design of fusion proteins by providing an appropriate spacing between domains and support the correct folding of the fusion polypeptide. In some embodiments, the fusion polypeptide may 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.

[0179] In some embodiments, the fusion polypeptide of the present disclosure may include a structured sequence region from a first apolipoprotein fused to a structured sequence region of a second apolipoprotein, the first apolipoprotein may be APOE or APOA, and the second apolipoprotein may be APOE or APOA.

[0180] In some embodiments, the fusion polypeptide of the present disclosure may include structured sequence regions, N-terminal sequence regions, and C-terminal sequence regions each independently derived from the same or two or more apolipoproteins such as APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, APOO, or variants thereof.

[0181] In some embodiments, the fusion polypeptide may include one or more of regions, motifs, surface expressions, local conformational shapes, folds, loops, half-loops, domains, half-domains, sites, termini, or any combination thereof from parent proteins such as, but not limited to, APOE, APOA, APOB, APOC, APOD, APOF, APOH, APOJ, APOL, APOM, APOO, or variants thereof.

[0182] Polypeptide sequence In some embodiments, the apolipoprotein may comprise two or more polypeptide characteristic sequences disclosed herein. In some embodiments, the apolipoprotein sequence is the sequence disclosed in Table 8.

[0183]

Table 8-1

[0184]

Table 8-2

[0185]

Table 8-3

[0186]

Table 8-4

[0187]

Table 8-5

[0188]

Table 8-6

[0189]

Table 8-7

[0190]

Table 8-8

[0191]

Table 8-9

[0192]

Table 8-10

[0193]

Table 8-11

[0194]

Table 8-12

[0195]

Table 8-13

[0196]

Table 8-14

[0197] Lipid The compositions of the present disclosure may include one or more lipids. As used herein, the term "lipid" refers to a molecule of biological origin that is soluble in organic solvents (e.g., chloroform) but shows little or no solubility in water. In some embodiments, the compositions of the present disclosure may include derivatives of lipids. As used herein, the term "derivative" refers to a molecule that has been modified or changed in any way with respect to a reference molecule or starting molecule, e.g., a lipid.

[0198] 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, cardiolipin, or a glycerosphingolipid. In some embodiments, the lipid can be a cationic lipid, a fusogenic lipid, an anionic lipid, a neutral lipid, or any combination thereof.

[0199] The organ selectivity of the compositions of the present disclosure can be achieved, for example, by adjusting the ratio of lipids so as to target the spleen or the lung. As used herein, the term "lipid" is intended to encompass all stereoisomers, geometric isomers, tautomers, and isotopes of structures depicted or described in connection with lipids. When referring to a lipid feature or substituent, the term "optional" or "optionally" refers to a feature or substituent that may or may not occur. For example, "optionally substituted alkyl" encompasses both "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 groups are not intended to introduce any substitutions or substitution patterns that are not sterically realistic, synthetically infeasible, and / or inherently unstable. In some embodiments, isotopes of lipids can be utilized to facilitate their detection using mass spectrometry and / or to slow the oxidation rate of the lipids (see Shchepinov, M.S. (2007). Rejuvenation research, 10(1), 47-60, the content of which is hereby incorporated by reference in its entirety).

[0200] The lipids described herein can have an asymmetric center, a geometric center (e.g., a double bond), or both. Unless a specific stereochemical form or isomeric form is specifically indicated, all chiral, diastereomeric, racemic forms of the structure, and all geometric isomeric forms are intended. Lipids of the present disclosure containing asymmetrically substituted atoms can be isolated in optically active form or racemic form. Methods for preparing optically active forms, for example, by resolution of a racemic form, synthesis from optically active starting materials, or use of chiral auxiliaries, are well known in the art. Geometric isomers of olefins, C=N double bonds, or other types of double bonds may 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 may also exist and can be isolated as a mixture of isomers or as separated isomeric forms.

[0201] The lipids described herein also include tautomeric forms. Tautomeric forms result from the exchange of an adjacent double bond with a single bond and the accompanying movement of a proton. Tautomeric forms include prototropic tautomers, which are protonation states of isomers having the same empirical formula and total charge. Examples of prototropic tautomers include keto-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, amide-imidic acid pairs, enamine-imine pairs, and cyclic forms in which a proton can occupy two or more positions in a heterocyclic system, such as 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in an equilibrium state or can be stereochemically fixed in one form by appropriate substitution.

[0202] The lipids described herein also encompass all isotopes of the atoms present in the intermediate or final compounds. "Isotope" refers to atoms that have the same atomic number but different mass numbers resulting from different numbers of neutrons in the nucleus. Thus, by way of 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, by way of example, each individual carbon atom present in formula (200) can exist as a 12 C, 13 C or 14 C atom.

[0203] In some embodiments, the compositions of the present disclosure may include derivatives of any of the lipids described herein (referred to herein as "lipid derivatives"). As used herein, the term "derivative" refers to a compound, for example a lipid, in which at least one atom or group is different from the parent compound, for example a form or version of the lipid.

[0204] In some embodiments, the lipid derivative may include a hydrophilic group. The term "hydrophilic" and its grammatical equivalents as used herein refer to a substance or structure having a polar group that readily interacts with water. In some embodiments, the lipid may include a hydrophobic group. The term "hydrophobic" and its grammatical equivalents as used herein refer to a substance or structure having a polar group that does not readily interact with water. For the structures provided herein, the following subscripts in parentheses further define the groups as follows. "(C n )" defines the exact number (n) of carbon atoms in the group. For example, "(C 2~10) Alkyl refers to those alkyl groups having 2 to 10 carbon atoms (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10), or any range derivable therefrom (e.g., 3 to 10 carbon atoms). In some embodiments, the lipid derivative may differ from a lipophilic substance by the inclusion of an alkyl group. The "alkyl" group may refer to an aliphatic hydrocarbon group. The alkyl moiety may be a "saturated alkyl" group, which means it does not contain an alkene or alkyne moiety. The alkyl moiety may also be an "unsaturated alkyl" moiety, which means it contains at least one alkene or alkyne moiety. In some embodiments, the lipid derivative may contain an alkene moiety. The "alkene" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon double bond. In some embodiments, the lipid derivative may contain an alkyne moiety. As used herein, the "alkyne" moiety refers to a group consisting of at least two carbon atoms and at least one carbon-carbon triple bond. The alkyl moiety can be branched, straight-chain, or cyclic, whether saturated or unsaturated. Further, the alkyl moiety, whether saturated or unsaturated, can include branched-chain, straight-chain, and / or cyclic moieties. Depending on the structure, the alkyl group can be a monoradical or a diradical (i.e., an alkylene group). In some embodiments, the lipid derivative may contain a heteroalkyl group. The "heteroalkyl" group is as described for "alkyl" in which at least one of its C atoms is substituted with an N, S, or O atom. The "heteroalkyl" group can include straight-chain, branched-chain, and / or cyclic moieties. In certain embodiments, "lower alkyl" is an alkyl group having 1 to 6 carbon atoms (i.e., C 1 ~C 6 alkyl group). In certain cases, "lower alkyl" can be straight-chain or branched-chain.

[0205] In some embodiments, the lipid derivative may contain an aryl group. In some aspects, the lipid derivative may be an aryl radical. An "aryl radical" refers to a radical derived from an aromatic monocyclic or polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. The aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen and carbon, contains 5 to 18 carbon atoms, and at least one of the rings within the ring system is aromatic, i.e., contains a cyclic delocalized (4n + 2)p electron system according to Hückel's theory. Ring systems from which aryl groups are derived include groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. In some embodiments, the term "aryl" can refer to an aromatic ring in which each of the atoms forming the ring is a carbon atom. The aryl ring can be formed by 5, 6, 7, 8, 9, or more than 9 carbon atoms. The aryl group in the lipid can be optionally substituted. Aryl groups include, but are not limited to, phenyl, naphthalenyl, phenanthrenyl, anthracenyl, fluorenyl, and indenyl. Depending on the structure, the aryl group can be a monoradical or a diradical (i.e., an arylene group).

[0206] In some embodiments, the lipid derivative may contain a heteroaryl moiety. A "heteroaryl radical" refers to a radical derived from a 3- to 12-membered aromatic ring radical containing 2 to 11 carbon atoms and at least one heteroatom, each heteroatom being optionally selected from N, O, and S. As used herein, the heteroaryl ring may be selected from monocyclic or bicyclic and fused or bridged ring systems, with at least one of the rings within the ring system being aromatic, i.e., containing a cyclic delocalized (4n + 2)p electron system according to Hückel's theory. The heteroatom(s) in the heteroaryl radical may optionally be oxidized. In some embodiments, the lipid derivative, if present, may contain one or more nitrogen atoms and is optionally quaternized. The heteroaryl may be attached to the remainder of the molecule via any atom of the heteroaryl, such as a carbon atom or a nitrogen atom of the heteroaryl, as long as the valence is permitted. The heteroaryl includes, but is not limited to, azepinyl group, acridinyl group, benzimidazolyl group, benzindolyl group, 1,3-benzodioxolyl group, benzofuranyl group, benzoxazolyl group, benz[d]thiazolyl group, benzothiadiazolyl group, benzo[b][1,4]dioxepinyl group, benzo[b][1,4]oxazinyl group, 1,4-benzodioxanyl, benzonaphthofuranyl group, benzoxazolyl group, benzodioxolyl group, benzodioxinyl group, benzopyranyl group, benzopyranonyl group, benzofuranyl group, benzofuranonyl group, benzothienyl (benzothiophenyl) group, benzothieno[3,2-d]pyrimidinyl group, benzotriazolyl group, benzo[4,6]imidazo[1,2-a]pyridinyl group, carbazolyl group, cinnolinyl group, cyclopenta[d]pyrimidinyl group, 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 group, dibenzothiophenyl group, furanyl group, furanonyl group, furo[3,2-c]pyridinyl group, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl group, 5,6,7,8,9,10 - hexahydrocycloocta[d]pyridazinyl group, 5,6,7,8,9,10 - hexahydrocycloocta[d]pyridinyl group, isothiazolyl group, imidazolyl group, indazolyl group, indolyl group, indazolyl group, isoindolyl group, indolinyl group, isoindolinyl group, isoquinolyl group, indolizinyl group, isoxazolyl group, 5,8 - methano - 5,6,7,8 - tetrahydroquinazolinyl group, naphthyridinyl group, 1,6 - naphthyridinonyl group, oxadiazolyl group, 2 - oxoazepinyl group, oxazolyl group, oxiranyl group, 5,6,6a,7,8,9,10,10a - octahydrobenzo[h]quinazolinyl group, 1 - phenyl - 1H - pyrrolyl group, phenazinyl group, phenothiazinyl group, phenoxazinyl group, phthalazinyl group, pteridinyl group, purinyl group, pyrrolyl group, pyrazolyl group, pyrazolo[3,4 - d]pyrimidinyl group, pyridinyl group, pyrido[3,2 - d]pyrimidinyl group, pyrido[3,4 - d]pyrimidinyl group, pyrazinyl group, pyrimidinyl group, pyridazinyl group, pyrrolyl group, quinazolinyl group, quinoxalinyl group, quinolinyl group, isoquinolinyl group, tetrahydroquinolinyl group, 5,6,7,8 - tetrahydroquinazolinyl group, 5,6,7,8 - tetrahydrobenzo[4,5]thieno[2,3 - d]pyrimidinyl group, 6,7,8,9 - tetrahydro - 5H - cyclohepta[4,5]thieno[2,3 - d]pyrimidinyl group, 5,6,7,8 - tetrahydropyrido[4,5 - c]pyridazinyl group, thiazolyl group, thiadiazolyl group, triazolyl group, tetrazolyl group, triazinyl group, thieno[2,3 - d]pyrimidinyl group, thieno[3,2 - d]pyrimidinyl group, thieno[2,3 - c]puridinyl group, and thiophenyl (i.e., thienyl) group. "X - membered heteroaryl" refers to the number of ring atoms within the ring, i.e., X. For example, a 5 - membered heteroaryl ring or a 5 - membered aromatic heterocyclic ring has 5 ring atoms within the ring, such as triazole, oxazole, thiophene, etc.,

[0207] In some embodiments, the term "heteroaryl", when used without the modifier "substituted", refers to a monovalent group having an aromatic carbon atom or a nitrogen atom as a point of attachment, where the carbon atom or nitrogen atom forms part of an aromatic ring structure and at least one of the ring atoms is nitrogen, oxygen or sulfur, and the monovalent group consists of 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, indazolylinyl, methylpyridyl, oxazolyl, phenylimidazolyl, pyridyl, pyrrolyl, pyrimidyl, pyrazinyl, quinolyl, quinazolinyl, quinoxalinyl, tetrahydroquinolinyl, thienyl, triazinyl, pyrrolopyridinyl, pyrrolopyrimidinyl, pyrrolopyrazinyl, pyrrolotriazinyl, pyrrolimidazolyl, chromenyl (where the point of attachment is one of the aromatic atoms), and chromanyl (where the point of attachment is one of the aromatic atoms). Substituted heteroaryl refers to a monovalent group having an aromatic carbon atom or a nitrogen atom as a point of attachment, where the carbon atom or nitrogen atom forms part of an aromatic ring structure and at least one of the ring atoms is nitrogen, oxygen or sulfur, and 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.

[0208] In some embodiments, any of the moieties in the lipid may be substituted. The term "substituted" refers to a moiety having a substituent on one or more carbons of the structure or a replaceable heteroatom, such as a hydrogen-replacing substituent on NH. "Substituted" or "substituted with" is understood to imply that such substitution follows the allowed valences of the substituted atoms and substituents and that the substitution results in a stable compound, i.e., a compound that does not undergo spontaneous transformation, such as rearrangement, cyclization, elimination, etc. In certain embodiments, substituted refers to a moiety having 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, imino, or thioxo group. As used herein, the term "substituted" is intended to include all acceptable substituents of organic compounds. In broad aspects, acceptable substituents include substituents of acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic organic compounds. Acceptable substituents may be one or more and may be the same or different for a suitable organic compound. For the purposes of this disclosure, a heteroatom such as nitrogen may have a hydrogen substituent and / or any acceptable substituent of the organic compounds described herein that satisfies the valence of the heteroatom. In some embodiments, the substituent is any of the substituents described herein, such as halogen, hydroxy, oxo (=O), thioxo (=S), cyano (-CN), nitro (-NO 2 ), imino (=N-H), oximo (=N-OH), hydrazino (=N-NH 2 ), -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 , -Rb -C(O)N(R a ) 2 、-R b -O-R 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 (where t is 1 or 2), and alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl (any of these, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO 2 )、imino(=N-H), oxime(=N-OH), hydrazine(=N-NH 2 )、-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)Ra , -R b , -C(O)OR a , -R b , -C(O)N(R a ) 2 , -R b , -O-R 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 , -S(O) a (where t is 1 or 2) and -R b , -S(O) t , -S(O) a ) 2 (where t is 1 or 2) may be optionally substituted, wherein each R a is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, or heteroarylalkyl, and each R a is, as far as the valence allows, alkyl, alkenyl, alkynyl, halogen, haloalkyl, haloalkenyl, haloalkynyl, oxo(=O), thioxo(=S), cyano(-CN), nitro(-NO 2 ), imino(=N-H), oximo(=N-OH), hydrazine(=N-NH 2 ), -R b , -OR a , -R b , -OC(O)-R a , -R b , -OC(O)-OR a , -R b , -OC(O)-N(Ra ) 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 -O-R 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 (wherein, t is 1 or 2), -R b -S(O) t R a (wherein, t is 1 or 2), -R b -S(O) t OR a (wherein, t is 1 or 2) and -R b -S(O) t N(R a ) 2 (wherein, t is 1 or 2) is optionally substituted, and wherein each R b is independently selected from a direct bond or a linear or branched alkylene, alkenylene, or alkynylene chain, and each R c is a linear or branched alkylene, alkenylene, or alkynylene chain.

[0209] In some embodiments, the lipids of the present disclosure may be modified. The modification can be carried out to modify the properties of the lipids and / or compositions of the present disclosure. For example, the modification can be carried out to enhance specificity for a particular target tissue, change potency, improve the rate and extent of absorption, reduce toxicity, and change physical or chemical properties (e.g., solubility) to provide desired characteristics.

[0210] In some embodiments, the lipids of the present disclosure may be modified to include polar functional groups such as alcohols, amines, amides, carboxylic acids, sulfonic acids, and phosphate groups, which may be ionized or form relatively strong intermolecular attractions (hydrogen bonds) with water. In some embodiments, weak polar groups such as carboxylic acid esters, aryl halides, and alkyl halides may be incorporated into the lipids of the present disclosure to enhance lipid solubility.

[0211] In some embodiments, the lipids of the present disclosure may be modified to include reversibly and irreversibly bound groups. For example, groups that are directly bound to the carbon backbone of the lipid by C-C, C-O, and C-N bonds tend to be irreversible. Alternatively, groups that are linked to the lipid by ester, amide, phosphate, sulfate, and glycoside bonds may typically be more reversible.

[0212] In some embodiments, the compositions of the present disclosure may include biologically active lipids. In some embodiments, the compositions may be used to transport biologically active lipids from one site to another. In some embodiments, the compositions of the present disclosure may be used to transport biologically active lipids from one site of a subject to another site of the subject.

[0213] Lipids can include fats, waxes, steroids, cholesterol, fat-soluble vitamins, monoglycerides, diglycerides, triglycerides, phospholipids, sphingolipids, glycolipids, cationic or anionic lipids, derivatized lipids, and the like. In some embodiments, the lipids can form micelles, monolayers, and bilayer membranes. In some embodiments, the lipids can self-assemble into lipoprotein systems in combination with other components.

[0214] In some embodiments, the lipid may include one or more hydrophobic groups. As used herein, the term "hydrophobic group" refers to a chemical moiety that is water-insoluble 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 such as polystyrene and polyisoprene. In some embodiments, the lipid may include one or more hydrophilic groups. As used herein, the term "hydrophilic group" refers to a chemical moiety that is water-soluble 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 having both a hydrophobic moiety and a hydrophilic moiety. For example, an amphiphilic compound may have one hydrophilic face and one hydrophobic face. Amphiphilic compounds include, but are not limited to, cholic acid and cholic acid analogs and derivatives, and cholesteryl formate. In some embodiments, the compositions of the present disclosure include toxic lipid species. In some embodiments, the compositions of the present disclosure include protective lipid species. In some embodiments, the biologically active lipid includes polyunsaturated fatty acids, fat-soluble antioxidants, cholesteryl 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, cholesteryl esters such as cholesteryl oleate, triglycerides such as triolein, and the like. 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 cholesteryl esters. In some embodiments, the cholesteryl ester is cholesteryl oleate.In some embodiments, the compositions of the present disclosure include triglycerides. In some embodiments, the triglyceride may be triolein.

[0215] In some embodiments, the lipid provides a membrane environment in which cholesterol can be solubilized. In some embodiments, cholesterol can be actively effluxed by the ABC family of transporters. In some embodiments, cholesterol can be passively absorbed from cell membranes and / or lipid-rich debris. In some embodiments, passive absorption of lipid-rich debris can reduce microglial activation or neuroinflammation. For example, in some embodiments, microglia that phagocytose lipid-rich fragments can be filled with lipid droplets, including those rich in cholesteryl esters. In some embodiments, stimulation of microglial cholesterol efflux by exogenous lipoprotein can enhance microglial phagocytosis. In some embodiments, the relative affinity of lipoprotein for the extracellular matrix and receptors can modulate the balance between cholesterol efflux (lipid removal) and lipid delivery. In some embodiments, cholesterol is transported between cells (e.g., effluxed from astrocytes and delivered to neurons or oligodendrocytes) and can promote cell membrane growth, myelination / remyelination, synaptogenesis, and vesicle release. In some embodiments, another lipid delivered to cells containing phospholipids, cholesteryl esters, and triglycerides can provide an energy source and modify the metabolic state of the recipient cells. In some embodiments, monounsaturated fatty acid acyl chains (e.g., oleate), as well as deuterated polyunsaturated fatty acid acyl chains (e.g., DHA deuterated at the bis-allylic position (see Yang et al. (PNAS, 2016, 113(34):E4966-E4975), the content of which is incorporated herein by reference)), can protect cells from oxidative stress and cell death.

[0216] The compositions of the present disclosure may include cationic lipids, zwitterionic lipids, neutral lipids, and anionic lipids. Suitable lipids may include fats, waxes, steroids, cholesterol, fat-soluble vitamins, monoglycerides, diglycerides, phospholipids, sphingolipids, glycolipids, cationic or anionic lipids, derivatized lipids, and the like. In some embodiments, the lipids may be phospholipids, lysolipids, cholesterol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, and PEGylated lipids.

[0217] In some embodiments, the phospholipids include, but are not limited to, phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS), 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), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoylphosphatidylethanolamine (POPE), palmitoyloleoylphosphatidylserine (POPS), palmitoyloleoylphosphatidylglycerol (POPG), dioleoylphosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoylphosphatidylethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoylphosphatidylethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, 1-stearoyl-2-oleoyl-phosphatidylethanolamine (SOPE), 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (trans DOPE), and cardiolipin. In some embodiments, the phospholipid can be a lysophospholipid containing only one fatty acid moiety bound to the glycerol subunit via an ester bond. In some embodiments, lipid extracts such as egg PC, heart extract, brain extract, liver extract, and soy PC are also contemplated.In some embodiments, the lipid 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 commonly known in the art.

[0218] 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, cholic acid, progesterone, cortisone, aldosterone, estradiol, testosterone, and dehydroepiandrosterone. In some embodiments, synthetic steroids and their derivatives are also contemplated. The compositions described herein may contain cationic lipids containing 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-dioleyloxy)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]-N,N-dimethyl-N-hydroxyethylammonium bromide (DMRIE), N-[1-(2,3,dioleyloxy)propyl]-N,N-dimethyl-N-hydroxyethylammonium bromide (DORIE), 3 beta-[N-(N′,N′-dimethylaminoaminoethane)carbamoyl]cholesterol (DC-Chol), dimethyldioctadecylammonium (DDAB), and N,N-dimethyl-2,3-dioleyloxy)propylamine (DODMA).

[0219] The compositions described herein may include a diacylglycerol backbone linked to a phosphate group and an anionic lipid containing a net negative charge. Anionic lipids include, but are not limited to, phosphatidic acid, phosphatidylglycerol (PG), phosphatidylserine (PS), phosphoinositide, phosphatidylinositol, phosphatidylinositol-4-phosphate (PtdIns(4)P), phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), and cardiolipin.

[0220] In some embodiments, the compositions described herein can include lipids, such as 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-dihexadecanoyl-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-phosphoglycero-3-phosphoglycerol (MPPG), and cholesterol. In some embodiments, the compositions described herein may include neutral lipids. In some embodiments, the neutral lipid can be any lipid including simple lipids, complex lipids, and derived lipids. Neutral lipids include, but are not limited to, phospholipids, glyceroglycolipids, sphingoglycolipids, sphingoids, and sterols.For example, examples of phospholipids include phosphatidylcholine (e.g., soy phosphatidylcholine, egg yolk phosphatidylcholine (EPC), distearoyl phosphatidylcholine (DSPC), dipalmitoyl phosphatidylcholine (DPPC), palmitoyl phosphatidylcholine (POPC), dimyristoyl phosphatidylcholine (DMPC), dioleoyl phosphatidylcholine (DOPC), etc.), phosphatidylethanolamine (e.g., distearoyl phosphatidylethanolamine (DSPE), dipalmitoyl phosphatidylethanolamine (DPPE), dioleoyl phosphatidylethanolamine (DOPE), dimyristoyl phosphoethanolamine (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, palmitoyloleoyl phosphatidylglycerol (POPG), lysophosphatidylcholine, etc.), sphingophospholipids (e.g., sphingomyelin, ceramide phosphoethanolamine, ceramide phosphoglycerol, ceramide phosphoglycerophosphate, etc.), glycerophospholipids, sphingophospholipids, natural lecithin (e.g., egg yolk lecithin, soy lecithin, etc.), and hydrogenated phospholipids (e.g., hydrogenated soy phosphatidylcholine, etc.), and other natural or synthetic phospholipids.

[0221] Examples of glyceroglycolipids in neutral lipids include sulfoxyribosyl glyceride, diglycosyl diglyceride, digalactosyl diglyceride, galactosyl diglyceride, and glycosyl diglyceride. Examples of sphingoglycolipids in neutral lipids include galactosyl cerebroside, lactosyl cerebroside, and ganglioside. Examples of sphingoids in neutral lipids include sphinganine,icosasphinganine, sphingosine, and their derivatives. Examples of sterols in neutral lipids include cholesterol, dihydrocholesterol, lanosterol, β-sitosterol, campesterol, stigmasterol, brassicasterol, ergosterol, fucosterol, and 3β-[N-(N’,N’-dimethylaminoethyl)carbamoyl]cholesterol (DC-Chol).

[0222] In some embodiments, the compositions described herein can include any combination of lipids. In some embodiments, the lipid composition can be adjusted to affect properties such as leakage rate, stability, particle size, zeta potential, protein binding, in vivo circulation, and / or accumulation in tissues or organs. For example, positive or negative lipids such as DSPG and / or DOTAP can be included to affect the surface charge of the lipoprotein systems described herein. In some embodiments, the lipid composition can include about 10 or fewer lipids, or about 5 or fewer lipids, or about 3 or fewer lipids. In some embodiments, the lipids can include at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 different lipids. In some embodiments, the mole percentage (mol%) of a particular type of lipid present can be about 0% to about 100%, about 10% to about 100%, about 20% to about 100%, about 30% to about 100%, about 50% to about 100%, about 60% to about 100%, or about 70% to 100%, about 80% to 100%, about 90% to 100% of all the lipids present in the compositions described herein. In some embodiments, the mole percentage (mol%) of a particular type of lipid present can be about 0% to about 90%, about 0% to about 80%, about 0% to about 70%, about 0% to about 60%, about 0% to about 50%, about 0% to about 40%, or about 0% to 30%, about 0% to 20%, about 0% to 10% of all the lipids present in the compositions described herein.

[0223] In some embodiments, the compositions of the present disclosure include lipids. In some embodiments, the compositions of the present disclosure include less than 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 include 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 species. In some embodiments, the compositions of the present disclosure include at least 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 include a maximum of 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 include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 lipid species.

[0224] Fatty acid 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 having long-chain hydrocarbon side groups.

[0225] In some embodiments, the fatty acid may be a free fatty acid. In some embodiments, the hydrocarbon side group (or chain) may have a carbon length of about 4 to about 36. In some embodiments, the lipid of the present disclosure may be a saturated fatty acid that may contain one carbon-carbon single bond. In some embodiments, the lipid of the present disclosure may be an unsaturated fatty acid that may contain one or more carbon-carbon double bonds. In some embodiments, the unsaturated fatty acid may be a monounsaturated fatty acid containing one carbon-carbon double bond. In some embodiments, the lipid of the present disclosure may 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, mead acid, eicosatrienoic acid, stearidonic acid, arachidonic acid, eicosatetraenoic acid, adrenic acid, bosseopentaenoic acid, eicosapentaenoic acid, osbond acid, sardinic acid, tetracosanolpentaenoic acid, cervonic acid, and / or arachidonic acid.

[0226] 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).

[0227] Wax In some embodiments, the lipid of the present disclosure may be or may include wax. As used herein, wax is a long-chain (C 16 ~ about C 30 ) alcohol having a long chain (about C 14 ~ about C 36It may refer to esters of saturated or unsaturated fatty acids. The wax may be water-insoluble and / or solid at biological temperatures. Examples of waxes are beeswax and cetyl palmitate.

[0228] Triacylglycerol In some embodiments, the lipid of the present disclosure may be or may include triacylglycerol. As used herein, the term triacylglycerol refers to a molecule that includes three fatty acids each esterified to a single glycerol.

[0229] Triacylglycerol may contain the same fatty acid at all three positions (also referred to as simple triacylglycerol) or may contain two or three different fatty acids. Glycerophospholipid In some embodiments, the lipid of the present disclosure may be or may include glycerophospholipid. As used herein, glycerophospholipid may refer to a lipid in which two fatty acids are ester-linked to the first and second carbons of glycerol and a highly polar or charged group may be linked to the third carbon of glycerol via a phosphodiester linkage. The fatty acids in glycerophospholipid may be any known fatty acids.

[0230] The lipid of the present disclosure may be represented by formula (I),

[0231]

Chemical formula

[0232] wherein, X 1 and X 2 are independently N, O, or absent, R 1 and R 2 are independently optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, or absent.

[0233] The glycerophospholipid may be phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, or phosphatidylglycerol.

[0234] In some embodiments, the glycerophospholipid may be phosphatidic acid in which the group bonded to the phosphorus atom in the glycerophospholipid is hydroxyl. In some embodiments, the phosphorus atom in the glycerophospholipid may be phosphatidylethanolamine, and the group bonded to the phosphorus atom in the glycerophospholipid may be ethanolamine. In some embodiments, the glycerophospholipid may be phosphatidylcholine, and the group bonded to the phosphorus atom in the glycerophospholipid may be choline. In some embodiments, the glycerophospholipid may be phosphatidylglycerol, and the group bonded to the phosphorus atom in the glycerophospholipid may be glycerol. In some embodiments, the glycerophospholipid may be phosphatidyl 4-5-bisphosphate, and the group bonded to the phosphorus atom in the glycerophospholipid may be myo-inositol 4,5-bisphosphate. In some embodiments, the glycerophospholipid may be cardiolipin, and the group bonded to the phosphorus atom in the glycerophospholipid may be phosphatidylglycerol.

[0235] In some embodiments, the glycerophospholipid may be an ether lipid or an ether-linked lipid that may have an alkyl chain bonded to the first carbon position by an ether bond. The moiety bonded to the phosphate group in the ether lipid may be choline, ethanolamine, inositol, or serine. Ether lipids may constitute about 20% of the total phospholipid pool in mammals, but the tissue distribution varies. The highest levels are found in the brain, heart, spleen, and white blood cells.

[0236] The glycerophospholipid may be a derivative of phosphatidic acid, phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine, or phosphatidylglycerol. In some embodiments, the lipid may be a derivative of a derivative of phosphatidylcholine. Phosphatidylcholine can be represented by formula (Ia).

[0237]

Chemical formula

[0238] Derivatives of phosphatidylcholine are 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or POPC), 1,2-ditetradecanoyl-sn-glycero-3-phosphocholine (1,2-dimyristoyl-sn-glycero-3-phosphocholine or DMPC), 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (dipalmitoyl phosphatidylcholine or DPPC), 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine (dioleoyl phosphatidylcholine or DOPC), 1-hexadecyl-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-pentadecenoyl)-sn-glycero-3-phosphocholine, 1-henicosanoyl-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-dioctadecanoyl-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z,15Z-henicosatetraenoyl)-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-didodecanoyl-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-henicosanoyl-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-(9Z,12Z-octadecadienoyl)-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,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine, 1-tetradecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, 1-tetradecanoyl-2-hexacosanoil-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, 1-hexadecanoyl-2-(9Z,11E,13E,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z,17Z - Eicosapentaenoyl)-sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2 - docosanoyl - sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2-(7Z,10Z,13Z,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 - hexacosanoyl - sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2-(5Z,9Z - hexacosanodienoyl)-sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2 - propionyl - sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2-(2E - propionyl)-sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2-(4E - valeryl)-sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2 - hexanoyl - sn - glycero - 3 - phosphocholine, 1-(2Z - hexadecenoil)-2-(9Z - octadecenoil)-sn - glycero - 3 - phosphocholine, 1,2 - di-(9E - hexadecenoil)-sn - glycero - 3 - phosphocholine, 1-(9Z - hexadecenoil)-sn - glycero - 3 - phosphocholine, 1,2 - di-(9Z - hexadecenoil)-sn - glycero - 3 - phosphocholine, 1-(9Z - hexadecenoil)-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-glycero-3-phosphocholine, 1-heptadecanoyl-2-nonanoyl-sn-glycero-3-phosphocholine, 1,2-di-(9Z,12Z-heptadecadienoyl)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-tetradecanoyl-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(13Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(9E-octadecenoyl)-sn-glycero-3-phosphocholine, 1-octadecanoyl-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, 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-eicosatrienoil)-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-octa, Decanoyl-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,19E-docosahexaenoyl)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-hexacosanyl-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-propionyl-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(2E-propionyl)-sn-glycero-3-phosphocholine, 1,2-di-(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-di-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoyl)-2-docosanoyl-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoyl)-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(13Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(14Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(16Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(2Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(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-di-(6Z,9Z-octadecadienoyl)-sn-glycero-3-phosphocholine, 1,2-di-(9Z,11Z-octadecadienoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12E-octadecadienoyl)-2-(9Z,11E-heptadecadienoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1-(9Z,12Z-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-di-(9E,11E,13E-octadecatrienoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(9E,11E,13E,15E-octadecatetraenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(9Z,11E,13E,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(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-eicosatrienoil)-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-hexacosanyl-sn-glycero-3-phosphocholine, 1-eicosanoyl-2-nonanoyl-sn-glycero-3-phosphocholine, 1,2-di-(11E-eicosenoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(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-docosanoil-sn-glycero-3-phosphocholine, 1-(8E,11E,14E,17E-eicosatetraenoyl)-2-hexadecanoyl-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-dihenicosanoyl-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-docosanoyl-sn-glycero-3-phosphocholine, 1-docosanoyl-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-docosanoyl-2-hexacosanyl-sn-glycero-3-phosphocholine, 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1-tricosanyl-2-octadecanoyl-sn-glycero-3-phosphocholine, 1,2-ditricosanyl-sn-glycero-3-phosphocholine, 1-tetracosanyl-2-octadecanoyl-sn-glycero-3-phosphocholine, 1-tetracosanyl-2-(6Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-tetracosanyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1,2-ditetracosanyl-sn-glycero-3-phosphocholine, 1,2-di-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine, 1-pentacosanyl-2-octadecanoyl-sn-glycero-3-phosphocholine, 1-propionyl-sn-glycero-3-phosphocholine, 1,2-dipropionyl-sn-glycero-3-phosphocholine, 1-dotriacontanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-tetratriacontanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1-hexatriacontanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1-butyryl-2-octadecanoyl-sn-glycero-3-phosphocholine, 1,2-dibutyryl-sn-glycero-3-phosphocholine, 1-valeryl-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-henicosanoyl-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,11, Z,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-propionyl-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-heptadecyl-2-heptadecanoyl-sn-glycero-3-phosphocholine, 1-heptadecyl-2-acetyl-sn-glycero-3-phosphocholine, 1-heptadecyl-2-eicosanoyl-sn-glycero-3-phosphocholine, 1-heptadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-heptadecyl-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-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-acetyl-sn-glycero-3-phosphocholine, 1-nonadecyl-2-docosanoyl-sn-glycero-3-phosphocholine, 2-tetradecanoyl-sn-glycero-3-phosphocholine, 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-valeryl-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-hexadecyl-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-nonadecyl-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]-ladanyl-hexanyl)-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-(8-[5]-ladanyl-octanyl)-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-(8-[3]-ladanyl-octanyl)-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-hexadecanoyl-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-(6-[5]-ladanyl-hexanoyl)-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-(8-[5]-ladanyl-octanoyl)-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-(6-[3]-ladanyl-hexanoyl)-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-(8-[3]-ladanyl-octanoyl)-2-(8-[3]-ladanyl-octanyl)-sn-glycerophosphocholine, 1-tetradecanoyl-2-(8-[3]-ladanyl-octanyl)-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-phytatrienyl)-2-(2E,6E,10E-phytatrienyl)-sn-glycero-3-phosphocholine, 1-(2E-phytanyl)-2-(2E-phytanyl)-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(4Z,7Z,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-pentadecenoyl)-glycero-3-phosphocholine, 1-dodecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-dodecanoyl-2-heptadecanoyl-glycero-3-phosphocholine, 1-dodecanoyl-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-dodecanoyl-2-nonadecanoyl-glycero-3-phosphocholine, 1-dodecanoyl-2-(9Z-nonadecenoyl)-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-henicosanoyl-glycero-3-phosphocholine, 1-tridecanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-tridecanoyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine, 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-nonadecanoyl-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-(13Z,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-pentadecenoyl)-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-hexadecanoyl-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-heptadecenoyl)-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-phospho, Choline, 1-pentadecanoyl-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-pentadecanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 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-docosanoyl-glycero-3-phosphocholine, 1-pentadecanoyl-2-(11Z-docosenoyl)-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-pentadecanoyl-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-octadecanoyl-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-eicosanoyl-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(5Z,8Z,11Z,14Z-Eicosatetraenoyl)-glycero-3-phosphocholine, 1-(9Z-Pentadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-Eicosapentaenoyl)-glycero-3-phosphocholine, 1-(9Z-Pentadecenoyl)-2-Heneicosanoyl-glycero-3-phosphocholine, 1-(9Z-Pentadecenoyl)-2-(13Z,16Z-Docosadienoyl)-glycero-3-phosphocholine, 1-Hexadecanoyl-2-Tridecanoyl-glycero-3-phosphocholine, 1-Hexadecanoyl-2-(9Z-Tetradecenoyl)-glycero-3-phosphocholine, 1-Hexadecanoyl-2-(9Z-Nonadecenoyl)-glycero-3-phosphocholine, 1-Hexadecanoyl-2-(11Z,14Z-Eicosadienoyl)-glycero-3-phosphocholine, 1-Hexadecanoyl-2-(11Z-Docosenoyl)-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-Pentadecenoyl)-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,15Z-octadecatetraenoyl)-glycero-3-phosphocholine, 1-heptadecanoyl-2-nonadecanoyl-glycero-3-phosphocholine, 1-heptadecanoyl-2-(9Z-nonadecenoil)-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-docosenoyl)-glycero-3-phosphocholine, 1-heptadecanoyl-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-docosanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-heptadecadienoyl)-2-dodecanoyl-glycero-3-phosphocholine, 1-(9Z,12Z-heptadecadienoyl)-2-tridecanoyl-glycero-3-phosphocholine, 1-(9Z,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 - pentadecenoyl)-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-(6Z,9Z,12Z - octadecatrienoyl)-glycero - 3 - phosphocholine, 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,14Z - eicosatetraenoyl)-glycero - 3 - phosphocholine, 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 - pentadecenoyl)-glycero - 3 - phosphocholine, 1 - octadecanoyl - 2-(9Z,12Z - heptadecadienoyl)-glycero - 3 - phosphocholine, 1 - octadecanoyl - 2-(9Z,12Z,15Z - octadecatrienoyl)-glycero - 3 - phosphocholine, 1 - octadecanoyl - 2 - nonadecanoyl - glycero - 3 - phosphocholine, 1 - octadecanoyl - 2-(9Z - nonadecenoil)-glycero - 3 - phosphocholine, 1 - octadecanoyl - 2 - heneicosanoyl - glycero - 3 - phosphocholine, 1 - octadecanoyl - 2-(13Z,16Z - docosadienoic acid)-glycero - 3 - phosphocholine, 1-(9Z - octadecenoil)-2 - heptadecanoyl - glycero - 3 - phosphocholine, 1-(9Z - octadecenoil)-2-(6Z,9Z,12Z - octadecatrienoyl)-glycero - 3 - phosphocholine, 1-(9Z - octadecenoil)-2-(9Z - nonadecenoil)-glycero - 3 - phosphocholine, 1-(9Z - octadecenoil)-2 - heneicosanoyl - glycero - 3 - phosphocholine, 1-(9Z - octadecenoil)-2-(11Z - docosenoyl)-glycero - 3 - phosphocholine, 1-(9Z - octadecenoil)-2-(13Z,16Z - docosadienoic acid)-glycero - 3 - phosphocholine, 1-(9Z - octadecenoil)-2-(7Z,10Z,13Z,16Z - docosatetraenoic acid)-glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2 - dodecanoyl - glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2-(9Z - pentadecenoil)-glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2-(9Z - octadecenoil)-glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2-(6Z,9Z,12Z - octadecatrienoyl)-glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2-(9Z,12Z,15Z - octadecatrienoyl)-glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2 - nonadecanoyl - glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2 - eicosanoyl - glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-2-(5Z,8Z,11Z,14Z,17Z - eicosapentaenoic acid)-glycero - 3 - phosphocholine, 1-(9Z,12Z - octadecadienoic acid)-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-pe, N-tetradecanoyl-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-pentadecenoyl)-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-heptadecenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(6Z,9Z,1-(9Z,12Z,15Z-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, 1-(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-docosatetraenoyl)-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-octadecenoyl)-glycero-3-phosphocholine, 1-(6Z,9Z,12Z,15Z - octadecatetraenoyl)-2-(6Z,9Z,12Z - octadecatrienoyl)-glycero - 3 - phosphocholine, 1-(6Z,9Z,12Z,15Z - octadecatetraenoyl)-2 - nonadecanoyl - glycero - 3 - phosphocholine, 1-(6Z,9Z,12Z,15Z - octadecatetraenoyl)-2-(9Z - nonadecenooyl)-glycero - 3 - phosphocholine, 1-(6Z,9Z,12Z,15Z - octadecatetraenoyl)-2 - heneicosanoyl - glycero - 3 - phosphocholine, 1-(6Z,9Z,12Z,15Z - octadecatetraenoyl)-2-(11Z - docosenoyl)-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, 1 - nonadecanoyl - 2-(9Z - octadecenooyl)-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 - nonadecenooyl)-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)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-pentadecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-octadecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecanoyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-docosanoyl-glycero-3-phosphocholine, 1-eicosanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-eicosanoyl-2-pentadecanoyl-glycero-3-phosphocholine, 1-eicosanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-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-docosenoyl)-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-tridecanoyl-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-pentadecanoyl-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(9Z-heptadecenoyl)-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-nonadecenoyl)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(5Z,8Z,11Z,14Z,17Z - Eicosapentaenoyl)-glycero-3-phosphocholine, 1-(11Z - Eicosenoyl)-2 - heneicosanoyl-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 - Docosa, Hexaenoyl)-glycero-3-phosphocholine, 1-(11Z,14Z-eicosadienoyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-(11Z,14Z-eicosadienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(11Z,14Z-eicosadienoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(11Z,14Z-eicosadienoyl)-2-octadecanoyl-glycero-3-phosphocholine, 1-(11Z,14Z-eicosadienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(11Z,14Z-eicosadienoyl)-2-(9Z-nonadecenoyl)-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-docosenoyl)-glycero-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-heptadecenoyl)-glycero-3-phosphocholine, 1-(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-eicosenoyl)-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(11Z-docosenoyl)-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, 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z-pentadecenoyl)-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)-glycero-3-phosphocholine, 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-nonadecenoyl)-glycero-3-phosphocholine, 1-(5Z,8Z,11Z,14Z - Eicosatetraenoyl)-2-(11Z - Eicosenoyl)-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 - Heneicosanoyl - 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 - glycero-3 - phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z - Eicosapentaenoyl)-2 - Pentadecanoyl - glycero-3 - phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z - Eicosapentaenoyl)-2-(9Z - Pentadecenoyl)-glycero-3 - phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z - Eicosapentaenoyl)-2-(9Z - Hexadecenoyl)-glycero-3 - phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z - Eicosapentaenoyl)-2-(9Z - Heptadecenoyl)-glycero-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 - Nonadecenoyl)-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-docosanoyl-glycero-3-phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-hexadecanoyl-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z-hexadecenoil)-glycero-3-phosphocholine, 1-heneicosanoyl-2-heptadecanoyl-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z-octadecenoil)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z-nonadecenoil)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-docosanoyl-2-(9Z-tetradecenoil)-glycero-3-phosphocholine, 1-docosanoyl-2-pentadecanoyl-glycero-3-phosphocholine, 1-docosanoyl-2-(9Z-pentadecenoil)-glycero-3-phosphocholine, 1-docosanoyl-2-hexadecanoyl-glycero-3-phosphocholine, 1-docosanoyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-docosanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-docosanoyl-2-nonadecanoyl-glycero-3-phosphocholine, 1-docosanoyl-2-(9Z-nonadecenoil)-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-docosenoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-eicosanoyl-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-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-pentadecenoyl)-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-(9Z-octadecenoil)-glycero-3-phosphocholine, 1-(13Z, 16Z-docosadienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-eicosanoyl-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 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-docosanoyl-glycero-3-phosphocholine, 1,2-di-(13Z,16Z-docosadienoyl)-sn-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-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-docosatetraenoyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(6Z,9Z,12Z - octadecatrienoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-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,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine, 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, 1-(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-octadecatrienoyl)-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-nonadecenoyl)-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-docosenoyl)-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-pentadecenoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-(11Z-docosenoyl)-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-nonadecenoyl)-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-eicosatrienoyl)-glycero-3-phosphocholine, 1-octadecyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-eicosyl-glycero-3-phosphocholine, 1-eicosyl-2-tridecanoyl-glycero-3-phosphocholine, 1-eicosyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-eicosyl-2-heptadecanoyl-glycero-3-phosphocholine, 1-eicosyl-2-(9Z-heptadecenoyl)-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-nonadecenoyl)-glycero-3-phosphocholine, 1-eicosyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-eicosyl-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-eicosyl-2-henicosanoyl-glycero-3-phosphocholine, 1-eicosyl-2-(11Z-docosenoyl)-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, 1-(1Z-hexadecenyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(9Z-heptadecenoyl)-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-nonadecenoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-eicosanoyl-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-docosanoyl-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(11Z-docosenoyl)-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-heptadecenoyl)-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(9Z,12Z-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-eicosenoyl)-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(8Z,11Z,14Z-eicosatrienoil)-glycer, L-α-phosphatidylcholine, 1-(1Z-octadecenyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-docosanoyl-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-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-eicosenyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-eicosanoyl-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(8Z,11Z,14Z-eicosatrienoil)-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-(11Z-docosenoyl)-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-docosenoyl)-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-docosenoyl)-sn-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-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,17Z-eicosatetraenoyl)-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-eicosatrienoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-eicosanoyl-2-(5Z,8Z,11Z-eicosatrienoyl)-sn-glycero-3-phosphocholine, 1-eicosanoyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-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-hexadecenoil)-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(11Z-octadecenoil)-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(9Z-octadecenoil)-sn-glycero-3-phosphocholine, 1-(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-eicosenoyl)-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(11Z-octadecenoil)-sn-glycero-3-phosphocholine, 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-tetradecanoyl-sn-glycero-3-phosphocholine, 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-(9Z-hexadecenoil)-sn-glycero-3-phosphocholine, 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine, 1-(13Z-docosenoyl)-2-(9Z-tetradecenoil)-sn-glycero-3-phosphocholine, 1-(13Z-docosenoyl)-2-(9Z-octadecenoil)-sn-glycero-3-phosphocholine, 1-(13Z-docosenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-sn-glycero-3-phosphocholine, 1-(13Z-docosenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine, 1-(13Z-docosenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-sn-glycero-3-phosphocholine, 1-(13Z-docosenoyl)-2-(5Z,8Z,11Z - Eicosatrienoyl)-sn - glycero - 3 - phosphocholine, 1-(13Z - Docosenoyl)-2-(8Z,11Z,14Z - Eicosatrienoyl)-sn - glycero - 3 - phosphocholine, 1-(13Z,16Z - Docosadienoyl)-2-(11Z - Octadecenoil)-sn - glycero - 3 - phosphocholine, 1-(7Z,10Z,13Z,16Z,19Z - Docosapentaenoyl)-2 - Tetradecanoyl - sn - glycero - 3 - phosphocholine, 1 - Tetracosanoyl - 2-(9Z,12Z - Octadecadienoyl)-sn - glycero - 3 - phosphocholine, 1-(15Z - Tetracosenoyl)-2-(9Z - Hexadecenoil)-sn - glycero - 3 - phosphocholine, 1-(15Z - Tetracosenoyl)-2 - Octadecanoyl - sn - glycero - 3 - phosphocholine, 1-(15Z - Tetracosenoyl)-2-(11Z - Octadecenoil)-sn - glycero - 3 - phosphocholine, 1-(15Z - Tetracosenoyl)-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 - Octadecenoil)-sn - glycero - 3 - phosphocholine, 1-(9Z - Octadecenyl)-2-(9Z,12Z - Octadecadienoyl)-sn - glycero - 3 - phosphocholine, 1-(9Z - Octadecenyl)-2 - Eicosanoyl - sn - 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 - Eicosenyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-docosyl-2-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine, 1-(13Z-docosenyl)-2-(13Z,16Z-docosadienoyl)-sn-glycero-3-phosphocholine, 1-(13Z-docosenyl)-2-(10Z,13Z,16Z-docosatrienoil)-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-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(5Z,8Z,11Z-eicosatri, Enoil)-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, 1-(1Z,9Z-octadecadienyl)-2-(13Z-docosenoyl)-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-tetracosaenoyl)-sn-glycero-3-phosphocholine, 1-(16Z,19Z,22Z,24Z,28Z,31Z-tetratriacontaahexaenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine, 1-(18Z,21Z,24Z,27Z,30Z-hexatriacontapentaenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine, 1-(21Z,24Z,27Z,30Z-hexatriacontatetraenoyl)-2-(5Z,8Z,11Z,14Z-Eicosatetraenoyl)-glycero-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-eicosaeynoyl)-sn-glycero-3-phosphocholine, 1-(Z)-alk-1-enyl-2-acyl-sn-glycero-3-phosphocholine, 1-(1Z-alkenyl)-sn-glycero-3-phosphocholine, 1-alkyl-2-acyl-sn-glycero-3-phosphocholine, 1-alkyl-sn-glycero-3-phosphocholine, 1-(10Z-heptadecenoyl)-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-henicosanoyl-sn-glycero-3-phosphocholine, 1-decanoyl-2-docosanoyl-sn-glycero-3-phosphocholine, 1-decanoyl-2-tricosanoyl-sn-glycero-3-phosphocholine, 1-decanoyl-2-tetracosanoil-sn-glycero-3-phosphocholine, 1-decanoyl-2-pentacosanoil-sn-glycero-3-phosphocholine, 1-decanoyl-2-butyryl-sn-glycero-3-phosphocholine, 1-undecanoyl-sn-glycero-3-phosphocholine, 1,2-Diundecanoyl-sn-glycero-3-phosphocholine, 1-Undecanoyl-2-eicosanoyl-sn-glycero-3-phosphocholine, 1-Undecanoyl-2-henicosanoyl-sn-glycero-3-phosphocholine, 1-Undecanoyl-2-tetracosanoyl-sn-glycero-3-phosphocholine, 1-Dodecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine, 1-Dodecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-Dodecanoyl-2-docosanoyl-sn-glycero-3-phosphocholine, 1-Dodecanoyl-2-hexacosanyl-sn-glycero-3-phosphocholine, 1,2-Ditridecanoyl-sn-glycero-3-phosphocholine, 1-Tridecanoyl-2-nonadecanoyl-sn-glycero-3-phosphocholine, 1-Tridecanoyl-2-pentacosanyl-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 - Di-(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 - pentadecanoyl - 2 - heneicosanoyl - 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 - heptadecenoyl)-sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2 - octadecanoyl - sn - glycero - 3 - phosphocholine, 1 - hexadecanoyl - 2-(11E - octadecenoyl)-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, 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-eicosatrienoil)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(5E,8E,11E,14E-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-(4E,7E,10E,13E,16E,19E-docosahexaenoyl)-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-tetracosanyl-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-butyryl-sn-glycero-3-phosphocholine, 1-hexadecanoyl-2-valeryl-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, 1,2-di-(2E,4E-hexadecadienoyl)-sn-glycero-3-phosphocholine, 1-(2E,4E-hexadecadienoyl)-2-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine, 1,2-diheptadecanoyl-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-di-(10Z-heptadecenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(9Z-heptadecenoyl)-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-octadeca, Lyso-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-eicosatrienoil)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(5Z,8Z,11Z-eicosatrienoil)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(8Z,11Z,14Z-eicosatrienoil)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-docosanoyl-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-octadecanoyl-2-(10Z,13Z,16Z-docosatrienoil)-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-octadecenoil)-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoil)-2-(13Z-eicosenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoil)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoil)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, 1,2-di-(12Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-di-(15Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-di-(17Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-di-(3Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-di-(6E-octadecenoil)-sn-glycero-3-phosphocholine, 1-(6Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-di-(6Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-di-(7Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-di-(9E-octadecenoil)-sn-glycero-3-phosphocholine, 1-(9E-octadecenoil)-2-acetyl-sn-glycero-3-phosphocholine, 1-(9E-octadecenoil)-2-eicosanoyl-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoil)-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoil)-2-(9Z-hexadecenoil)-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoil)-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,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine, 1-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine, 1,2-di-(2E,4E-octadecadienoyl)-sn-glycero-3-phosphocholine, 1,2-di-(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-di-(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-octadecatrienoyl)-sn-glycero-3-phosphocholine, 1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-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-Dinonadecanoyl-sn-glycero-3-phosphocholine, 1-Nonadecanoyl-2-acetyl-sn-glycero-3-phosphocholine, 1-Nonadecanoyl-2-pentacosanoyl-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-Dieicosanoyl-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-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine, 1-(13Z-eicosenoyl)-2-docosanoyl-sn-glycero-3-phosphocholine, 1,2-Di-(9E-eicosenoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(9Z-eicosenoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(11E,14E-eicosadienoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(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-eicosapentaenoyl)-sn-glycero-3-phosphocholine, 1-Heneicosanoyl-sn-glycero-3-phosphocholine, 1-Heneicosanoyl-2-undecanoyl-sn-glycero-3-phosphocholine, 1-Heneicosanoyl-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, 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-Di-(13E-docosenoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(4E,7E,10E,13E,16E,19E-docosahexaenoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1,2-Di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(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-Di-(5E,9E-hexacosadienoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(5E,9Z-hexacosadienoyl)-sn-glycero-3-phosphocholine, 1,2-Di-(5Z,9E-hexacosadienoyl)-sn-glycero-3-phosphocholine, 1-(5Z,9Z-hexacosadienoyl)-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1,2-Di-(5Z,9, Z-hexacosadienoyl)-sn-glycero-3-phosphocholine, 1,2-di-(6Z,9Z-hexacosadienoyl)-sn-glycero-3-phosphocholine, 1-butyryl-sn-glycero-3-phosphocholine, 1-butyryl-2-(9Z-octadecenoil)-sn-glycero-3-phosphocholine, 1,2-dibutyryl-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-henicosanoyl-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-henicosanoyl-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-butyryl-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-hexadecenoil)-sn-glycero-3-phosphocholine, 1-tetradecyl-2-octadecanoyl-sn-glycero-3-phosphocholine, 1-tetradecyl-2-(9Z-octadecenoil)-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-eicosatrienoil)-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-valeryl-sn-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(9Z-octadecenoyl)-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-heptadecyl-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-eicosapentaenoyl)-sn-glycero-3-phosphocholine, 1-octadecyl-2-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine, 1-octadecyl-2-(7Z,10Z,13Z,16Z,19Z-docosapentaenoyl)-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-nonadecyl-2-acetyl-sn-glycero-3-phosphocholine, 1-ethyl-2-acetyl-sn-glycero-3-phosphocholine, 1-eicosyl-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1-eicosyl-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-hexadecenyl)-sn-glycero-3-phosphocholine, 1-(9E-hexadecenyl)-sn-glycero-3-phosphocholine, 1-(9Z-hexadecenyl)-sn-glycero-3-phosphocholine, 1-heptadecyl-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]-Radalan-octanyl)-sn-glycero-3-phosphocholine, 1-(6-[3]-Radalan-hexanyl)-2-(8-[3]-Radalan-octanyl)-sn-glycerophosphocholine, 1-(10-Methylhexadecanoyl)-2-(8-[3]-Radalan-octanyl)-sn-glycerophosphocholine, 1-Tetradecanoyl-2-(8-[3]-Radalan-octanyl)-sn-glycerophosphocholine, 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-acetyl-sn-glycero-3-phosphocholine, 1-(2E,6E,10E,14E-Phytatetraenyl)-2-(2E,6E,10E,14E-Phytatetraenyl)-sn-glycero-3-phosphocholine, 1,2-Diphytanyl-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-Eicosatetraenoyl)-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-Octadecatrienoyl)-glycero-3-phosphocholine, 1-Dodecanoyl-2-(9Z,12Z,15Z-Octadecatrienoyl)-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-docosenoyl)-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-pentadecenoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-hexadecanoyl-glycero-3-phosphocholine, 1-tridecanoyl-2-(9Z-heptadecenoyl)-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,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-tridecanoyl-2-(6Z,9Z,12Z,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-docosanyl-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-nonadecenoyl)-glycero-3-phosphocholine, 1-tetradecanoyl-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-tetradecanoyl-2-henicosanoyl-glycero-3-phosphocholine, 1-tetradecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-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-octadecatrienoyl)-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-docosanoyl-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-(9Z-tetradecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-pentadecanoyl-2-dodecanoyl-glycero-3-phosphocholine, 1-pentadecanoyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-pentadecanoyl-2-(9Z,12Z - heptadecadienoyl)-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-docosadienoyl)-glycero-3-phosphocholine, 1-pentadecanoyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-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-pentadecenoyl)-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-docosanoyl-glycero-3-phosphocholine, 1-(9Z-pentadecenoyl)-2-(11Z-docosenoyl)-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 - heptadecadienoyl)-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-heptadecenoyl)-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-nonadecenoyl)-glycero-3-phosphocholine, 1-(9Z-hexadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-(9Z-hexadecenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(9Z-hexadecenoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(9Z-hexadecenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-(9Z-hexadecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-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-heptadecenoyl)-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-eicosatrienoil)-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-heptadecenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-dodecanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-tridecanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-tetradecanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-pentadecanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-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-octadecatrienoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-eicosanoyl-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 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-docosenoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine, 1-(9Z-heptadecenoyl)-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-heptadecenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-heptadecadienoyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(9Z,12Z-heptadecadienoyl)-2-(9Z-nonadecenoyl)-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-docosenoyl)-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-hept, Tadecanoyl-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-pentadecenoyl)-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-2-(9Z,12Z-heptadecadienoyl)-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,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoil)-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-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-pentadecanoyl-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-heptadecanoyl-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-nonadecenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-docosanoyl-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-dodecanoyl-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-tridecanoyl-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-tetradecanoyl-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-heptadecanoyl-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, 1,2-di-(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-nonadecenoyl)-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-docosenoyl)-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-pentadecenoyl)-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,1-(9Z,12Z,15Z-octadecatrienoyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-octadecanoyl-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(11Z-docosenoyl)-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, 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,1-(12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1,2-di-(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-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-docosatetraenoyl)-glycero-3-phosphocholine, 1-nonadecanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-nonadecanoyl-2-(9Z-pentadecenoyl)-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-heptadecenoyl)-glycero-3-phosphocholine, 1-nonadecanoyl-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-henicosanoyl-glycero-3-phosphocholine, 1-nonadecanoyl-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-dodecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl), -2-Tridecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-tetradecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1,2-di-(9Z-nonadecenoyl)-sn-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-eicosanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-(9Z-nonadecenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine, 1-eicosanoyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-eicosanoyl-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-eicosanoyl-2-heptadecanoyl-glycero-3-phosphocholine, 1-eicosanoyl-2-(9Z-heptadecenoyl)-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-nonadecenoil)-glycero-3-phosphocholine, 1-eicosanoyl-2-(8Z,11Z,14Z-eicosatrienoil)-glycero-3-phosphocholine, 1-eicosanoyl-2-henicosanoyl-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-tetradecanoyl-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(9Z-tetradecenoil)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(9Z-hexadecenoil)-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-eicosatrienoil)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-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-tetradecenoil)-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-heptadecenoyl)-glycero-3-phosphocholine, 1-(11Z,14Z-eicosadienoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine, 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-di-(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-henicosanoyl-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-docosahexaenoyl)-glycero-3-phosphocholine, 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-pentadecenoyl)-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z-hexadecenoil)-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-octadecenoil)-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-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-nonadecenoil)-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1,2-di-(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,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 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-heptadecenoyl)-glycero-3-phosphocholine, 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(9Z,12Z-heptadecadienoyl)-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-eicosadienoyl)-glycero-3-phosphocholine, 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-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,17Z-eicosapentaenoyl)-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 - 3 - phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z - eicosapentaenoyl)-2-(6Z,9Z,12Z - octadecatrienoyl)-glycero - 3 - phosphocholine, 1-(5Z,8Z,11Z,14Z,1, 7Z-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-di-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-heneicosanoyl-glycero-3-phosphocholine, 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-heneicosanoyl-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-pentadecanoyl-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-heneicosanoyl-2-(6Z,9Z,12Z,15Z - octadecatetraenoyl)-glycero - 3 - phosphocholine, 1 - heneicosanoyl - 2 - nonadecanoyl - glycero - 3 - phosphocholine, 1 - heneicosanoyl - 2 - eicosanoyl - glycero - 3 - phosphocholine, 1 - heneicosanoyl - 2-(11Z,14Z - eicosadienoyl)-glycero - 3 - phosphocholine, 1 - heneicosanoyl - 2-(5Z,8Z,11Z,14Z - eicosatetraenoyl)-glycero - 3 - phosphocholine, 1 - heneicosanoyl - 2-(5Z,8Z,11Z,14Z,17Z - eicosapentaenoyl)-glycero - 3 - phosphocholine, 1 - heneicosanoyl - 2 - docosanoyl - glycero - 3 - phosphocholine, 1 - heneicosanoyl - 2-(13Z,16Z - docosadienoyl)-glycero - 3 - phosphocholine, 1 - heneicosanoyl - 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 - heptadecenoyl)-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 - heneicosanoyl - 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-docosenoyl)-2-pentadecanoyl-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-octadecanoyl-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1,2-di-(11Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine, 1-(11Z-docosenoyl)-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-heptadecenoyl)-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-nonadecenoyl)-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-docosenoyl)-glycero-3-phosphocholine, 1-(13Z,16Z-docosadienoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-tetradecanoyl-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z-tetradecenoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-octadecanoyl-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z-octadecenoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-nonadecanoyl-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(9Z-nonadecenoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(8Z,11Z,14Z-eicosatrienoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-henicosanoyl-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-docosanoyl-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(11Z-docosenoyl)-glycero-3-phosphocholine, 1,2-di-(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-pentadecenoyl)-glycero-3-phosphocholine, 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(9Z,12Z-heptadecadienoyl)-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-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, Phosphorus, 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-docosanyl-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-heptadecenoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-hexadecyl-2-henicosanoyl-glycero-3-phosphocholine, 1-hexadecyl-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-octadecyl-2-dodecanoyl-glycero-3-phosphocholine, 1-octadecyl-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-octadecyl-2-(9Z-heptadecenoyl)-glycero-3-phosphocholine, 1-octadecyl-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-octadecyl-2-(9Z-octadecenoyl)-glycero-3-phosphocholine, 1-octadecyl-2-(9Z,12Z-octadecadienoyl)-glycero-3-phosphocholine, 1-octadecyl-2-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-glycero-3-phosphocholine, 1-octadecyl-2-nonadecanoyl-glycero-3-phosphocholine, 1-octadecyl-2-henicosanoyl-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, 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-eicosatrienoil)-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-hexadecanoyl-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(9Z,12Z,15Z-octadecatrienoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(11Z-eicosenoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(1Z-hexadecenyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(9Z-pentadecenoyl)-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(9Z-hexadecenoyl)-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-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-nonadecenoyl)-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-pentadecenoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-hexadecanoyl-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-heptadecanoyl-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(9Z-heptadecenoyl)-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-nonadecenoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(11Z,14Z-eicosadienoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(13Z,16Z-docosadienoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-glycero-3-phosphocholine, 1-(1Z-eicosenyl)-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,13Z,16Z-docosapentaenoyl)-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-hexadecenoil)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-(9Z-hexadecenoil)-2-(7Z,10Z,13Z,16Z-docosapentaenoyl)-sn-glycero-3-phosphocholine, 1-(9Z-hexadecenoil)-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-docosenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoyl)-2-(7Z,10Z,13Z,16Z-docosatetraenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoyl)-2-tetracosanyl-sn-glycero-3-phosphocholine, 1-(11Z-octadecenoyl)-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(9Z-octadecenoyl)-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12Z-octadecadienoyl)-2-tetracosanoyl-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z-octadecatrienoyl)-2-(15Z-tetracosenoyl)-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-eicosatrienoil)-sn-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(9Z,12Z,15Z-octadecatrienoyl)-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(6Z,9Z,12Z,15Z-octadecatetraenoyl)-2-tetracosanoyl-sn-glycero-3-phosphocholine, Lysero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-(11Z-eicosenoyl)-2-(13Z-docosenoyl)-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-eicosatrienoyl)-2-(9Z-tetradecenoyl)-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z-eicosatrienoyl)-2-octadecanoyl-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-octadecatrienoyl)-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z-eicosatrienoyl)-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(8Z,11Z,14Z-eicosatrienoyl)-2-(13Z-docosenoyl)-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-glycero-3-phosphocholine, 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-eicosanoyl-sn-glycero-3-phosphocholine, 1-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-2-docosanoyl-sn-glycero-3-phosphocholine, 1-(5Z,8Z,11Z,14Z,17Z-eicosapentaenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-docosanoyl-2-(8Z,11Z,14Z,17Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine, 1-(13Z-docosenoyl)-2-tetradecanoyl-sn-glycero-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-(11Z-eicosenoyl)-sn-glycero-3-phosphocholine, 1-(7Z,10Z,13Z,16Z-docosatetraenoyl)-2-(11Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(4Z,7Z,10Z,13Z,16Z-docosapentaenoyl)-2-tetradecanoyl-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-octadecatetraenoyl)-sn-glycero-3-phosphocholine, 1-(15Z-tetracosenoyl)-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine, 1-(15Z-tetracosenoyl)-2-(6Z,9Z,12Z-octadecatrienoyl)-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-octadecyl-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-octadecadienoyl)-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-tetracosanoyl-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-docosenyl)-2-(13Z,16Z-docosadienoyl)-sn-glycero-3-phosphocholine, 1-(13Z,16Z-docosenyl)-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-tetracosenoyl)-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, 1-(1Z,11Z-octadecadienyl)-2-(11Z,14Z-eicosadienoyl)-sn-glycero-3-phosphocholine, 1-(1Z,11Z-octadecadienyl)-2-(13Z-docosenoyl)-sn-glycero-3-phosphocholine, 1-(1Z,11Z-octadecadienyl)-2-(13Z,16Z-docosadienoyl)-sn-glycero-3-phosphocholine, 1-(1Z,11Z-octadecadienyl)-2-tetracosanoyl-sn-glycero-3-phosphocholine, 1-(1Z,11Z-octadecadienyl)-2-(15Z-tetracosenoyl)-sn-glycero-3-phosphocholine, 1-(1Z,9Z-octadecadienyl)-2-(9Z-hexadecenoyl)-sn-glycero-3-phosphocholine, 1-(1Z,9Z-octadecadienyl)-2-octadecanoyl-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-docosenoyl)-sn-glycero-3-phosphocholine, 1-(14Z,17Z,20Z,23Z,26Z,29Z-dotriacontahexaenoyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycero-3-phosphocholine, 1-O-(2-methoxyhexadecyl)-sn-glycerol-3-phosphocholine, 1-O-(2-methoxy-4Z-hexadecenyl)-sn-glycero-3-phosphocholine, 1-undecanoyl-2-hexadecanoyl-sn-glycero-3-phosphocholine, 1...

Claims

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

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

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

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

5. The APOE contains one or more mutations with respect to the amino acid sequence corresponding to SEQ ID NO: 1 or SEQ ID NO: 268, and the one or more mutations are 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), 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 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 ID NO: 442), L89S (SEQ ID NO: 443), K90E (SEQ ID NO: 444), K90N (SEQ ID NO: 445), Y92C (SEQ ID 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 ID NO: 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 (SEQ ID 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 ID NO: 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 (SEQ ID 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 ID NO: 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 (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 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 (SEQ ID 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 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 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* (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 (SEQ ID 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 ID NO: 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 (SEQ ID 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 (SEQ ID 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), G183A (SEQ ID NO: 618), and combinations thereof, a lipoprotein system according to any one of claims 1 to 4, selected from the list.

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

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

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

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

10. The lipoprotein system according to claim 9, wherein the APOE comprises two or more structured sequence regions.

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

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

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

14. The one or more post-translational modifications are selected from the list of oxidation, carbamylation, oxycarbamylation, acetylation, phosphorylation, ubiquitination, biotinylation, carboxylation, deamidation, deamination, deacetylation, dihydroxylation, dephosphorylation, formylation, gamma-carboxyglutamidation, glutathionylation, glycylation, hydroxylation, methylation, nitration, sumoylation, N- or O-transglutamination, glycosylation, and farnesylation, the lipoprotein system according to claim 13.

15. The APOE includes an oxidatively linked dimer, the dimer including two APOE monomers, the lipoprotein system according to any one of claims 1 to 14.

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

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

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

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

20. The lipid includes formula (I), 【Chemical Formula 1】 wherein, X １ and X ２ are each independently N, O, or absent, R １ and R ２ are, independently, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, or absent, R ３ is 【Chemical Formula 2】 selected from, the lipoprotein system according to any one of claims 1 to 19.

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

22. The lipid is a lysolipid, the lipoprotein system according to any one of claims 1 to 21.

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

24. 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), and the lipoprotein system according to claim 23.

25. The lipid is phosphatidylcholine, and the lipoprotein system according to any one of claims 1 to 22.

26. 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), and the lipoprotein system according to claim 25.

27. The lipid is phosphatidylserine, and the lipoprotein system according to any one of claims 1 to 22.

28. 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), and the lipoprotein system according to claim 27.

29. The lipid contains at least two unique lipids, and the lipoprotein system according to any one of claims 1 to 28.

30. The at least two unique lipids include a first lipid and a second lipid, and the lipoprotein system according to claim 29.

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

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

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

34. The lipoparticle system according to any one of claims 1 to 33, wherein the APOE and the lipid are in a molar ratio of about 1:10,000 APOE to lipid to about 1:1 APOE to lipid.

35. The lipoparticle system according to any one of claims 1 to 34, wherein the APOE and the lipid are in a molar ratio of about 1:500 APOE to lipid to about 1:30 APOE to lipid.

36. The lipoparticle system according to any one of claims 1 to 35, wherein the APOE and the lipid are in a molar ratio of about 1:200 APOE to lipid to about 1:50 APOE to lipid.

37. The lipoparticle system according to any one of claims 1 to 36, wherein the APOE and the lipid are in a molar ratio of about 1:100 APOE to lipid.

38. The lipoparticle system according to any one of claims 1 to 37, wherein the system has a discoidal, spherical, cylindrical, lamellar, or elliptical morphology.

39. The lipoparticle system according to any one of claims 1 to 38, wherein the system has a discoidal morphology.

40. The lipoparticle system according to any one of claims 1 to 39, wherein the system has a diameter of 1 nm to 100 nm.

41. The lipoparticle system according to any one of claims 1 to 40, wherein the system has a maximum polydispersity percentage of 25%.

42. The lipoparticle system according to any one of claims 1 to 41, wherein the system has a maximum polydispersity percentage of 20%.

43. The lipoparticle system according to any one of claims 1 to 42, wherein the system has a maximum polydispersity percentage of 15%.

44. The lipoparticle system according to any one of claims 1 to 43, wherein the system has a maximum polydispersity percentage of 10%.

45. The lipoparticle system according to any one of claims 1 to 44, wherein the system has a maximum polydispersity percentage of 5%.

46. The lipoparticle system according to any one of claims 1 to 45, further comprising a payload.

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

49. The lipoprotein system according to claim 47 or 48, wherein the small molecule is selected from the group consisting of an antioxidant, an antitumor agent, an analgesic, an anesthetic, an antibacterial agent, an antispasmodic agent, an anti-dementia agent, an antidepressant, an antiemetic, an antifungal agent, an antigout agent, an anti-inflammatory agent, an antimigraine agent, an anti-myasthenia agent, an antimicrobial agent, an antiparasitic agent, an anti-Parkinson agent, an antipsychotic agent, an antispastic agent, an antiviral agent, an anxiolytic, a bipolar agent, a blood glucose regulator, a blood product, a blood regulator, a blood volume expander, a chemotherapeutic agent, a cardiovascular agent, a central nervous system agent, a dental oral agent, a skin agent, an electrolyte, an enzyme replacement agent, an enzyme regulator, a gastrointestinal agent, a genitourinary agent, an immune agent, an inflammatory bowel disease agent, a metabolic bone disease agent, an ophthalmic agent, an otic agent, a respiratory agent, a sedative, a hypnotic, and a skeletal muscle relaxant.

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

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

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

53. The lipoprotein system according to any one of claims 1 to 51, further comprising a lipoprotein system modifier.

54. The lipoprotein system according to claim 53, wherein the lipoprotein system modifier is a targeting agent, a regulator, a solubilizing agent, a stabilizing agent, or a detecting agent.

55. A method for treating or preventing a disease or disorder in a subject, the method comprising administering the lipoprotein system according to any one of claims 1 to 54.

56. The method according to claim 55, wherein the disease, injury, or disorder 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, cancer, or a multi-system disease.

57. The method according to claim 55 or 56, wherein the disease, injury, or disorder is a neurological disease.

58. The method according to any one of claims 55 to 57, wherein the disease, injury, or disorder is selected from one or more of degenerative cervical myelopathy, Niemann-Pick disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, Smith-Lemli-Opitz syndrome (SLOS), multiple system atrophy, prion disease, cognitive impairment, or dementia.

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

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

61. The method according to claim 57, wherein the neurological disease is coronavirus disease 2019 (COVID-19), or a neurological disease caused by COVID-19.

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