Novel secretory signal peptides and uses thereof

Abstract

Provided for herein are novel secretory signal peptides, recombinant polypeptides comprising the same, nucleic acid molecules encoding the same, pharmaceutical compositions comprising the same, and methods of use thereof.

Description

Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT NOVEL SECRETORY SIGNAL PEPTIDES AND USES THEREOF Related Applications

[0001] This application claims the benefit of U.S. Provisional Application Ser. No.63 / 584,695 filed September 22, 2023, and of U.S. Provisional Application Ser. No. 63 / 603,581 filed November 28, 2023, each of which is hereby incorporated by reference in its entirety. Sequence Listing

[0002] This application contains references to amino acid sequences and / or nucleic acid sequences which have been submitted concurrently herewith as the sequence listing xml file entitled “823037_sequencelisting.xml”, file size 36,864 bytes, created on September 20, 2024. The aforementioned sequence listing is hereby incorporated by reference in its entirety pursuant to 37 C.F.R. §1.52(e)(5). Field

[0003] The present disclosure relates generally to novel signal peptides and more particularly to novel secretory signal peptides for directing an encoded protein to be exported from the cell. Background

[0004] Recent scientific discoveries have highlighted the innumerable therapeutic applications of mRNA due to its modular nature and ability to provide customizable “instructions” to create functional proteins. Clinical studies continue to confirm its favorable efficacy, further underscoring its potential as a next-generation genetic medicine wherein scientists have only begun to scratch the surface of potential applications. Most of the research focus so far has been on amplifying intracellular expression of the encoded polypeptide. However, less focus has been placed on post-translational control of encoded proteins and targeted localization and / or secretion of the protein within the body.

[0005] Within the cell, a variety of unique avenues and processes exist that allow for the shuttling of proteins to various organelles as well as the export of proteins into the extracellular space via excretion pathways. However, in order to take advantage of these transport systems, the mRNA encoding each protein must also contain a metaphorical shipping label upstream from the protein sequence known as a signal peptide (SP). Design of novel SP for therapeutic mRNA could greatly benefit delivery, localization, and clearance of an encoded therapeutic protein. The present disclosure addresses these needs and others. ACTIVE / 131743364.1 1Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT Summary

[0006] In some embodiments, a signal peptide is provided. In some embodiments, the signal peptide comprises an amino acid sequence selected from the group consisting of Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX. XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, or XXXIII; wherein Formula I is represented as: A1-A2-A3-A4-A5(Formula I) and the identities of A1-A5are as provided in Table 2; wherein Formula II is represented as: B1-B2-B3-B4-B5-B6-B7-B8-B9-B10-B11-B12-B13-B14-B15(Formula II) and the identities of B1-B15are as provided in Table 3; wherein Formula III is represented as: C1-C2-C3-C4-C5-C6-C7-C8-C9-C10-C11-C12-C13-C14-C15-C16(Formula III) and the identities of C1-C16are as provided in Table 4; wherein Formula IV is represented as: D1-D2-D3-D4-D5-D6-D7-D8-D9-D10-D11-D12-D13-D14-D15-D16-D17(Formula IV) and the identities of D1-D17are as provided in Table 5; wherein Formula V is represented as: E1-E2-E3-E4-E5-E6-E7-E8-E9-E10-E11-E12-E13-E14-E15-E16-E17-E18(Formula V) and the identities of E1-E18are as provided in Table 6; wherein Formula VI is represented as: F1-F2-F3-F4-F5-F6-F7-F8-F9-F10-F11-F12-F13-F14-F15-F16-F17-F18-F19(Formula VI) and the identities of F1-F19are as provided in Table 7; wherein Formula VII is represented as: G1-G2-G3-G4-G5-G6-G7-G8-G9-G10-G11-G12-G13-G14-G15-G16-G17-G18-G19-G20 (Formula VII) and the identities of G1-G20are as provided in Table 8; wherein Formula VIII is represented as: H1-H2-H3-H4-H5-H6-H7-H8-H9-H10-H11-H12-H13-H14-H15-H16-H17-H18-H19-H20-H21(Formula VIII) and the identities of H1-H21are as provided in Table 9; wherein Formula IX is represented as: I1-I2-I3-I4-I5-I6-I7-I8-I9-I10-I11-I12-I13-I14-I15-I16-I17-I18-I19-I20-I21-I22(Formula IX) and the identities of I1-I22are as provided in Table 10; wherein Formula X is represented as: ACTIVE / 131743364.1 2Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT J1-J2-J3-J4-J5-J6-J7-J8-J9-J10-J11-J12-J13-J14-J15-J16-J17-J18-J19-J20-J21-J22-J23(Formula X) and the identities of J1-J23are as provided in Table 11; wherein Formula XI is represented as: K1-K2-K3-K4-K5-K6-K7-K8-K9-K10-K11-K12-K13-K14-K15-K16-K17-K18-K19-K20-K21-K22-K23- K24(Formula XI) and the identities of K1-K24are as provided in Table 12; wherein Formula XII is represented as: L1-L2-L3-L4-L5-L6-L7-L8-L9-L10-L11-L12-L13-L14-L15-L16-L17-L18-L19-L20-L21-L22-L23-L24-L25 (Formula XII) and the identities of L1-L25are as provided in Table 13; wherein Formula XIII is represented as: M1-M2-M3-M4-M5-M6-M7-M8-M9-M10-M11-M12-M13-M14-M15-M16-M17-M18-M19-M20-M21- M22-M23-M24-M25-M26(Formula XIII) and the identities of M1-M26are as provided in Table 14; wherein Formula XIV is represented as: N1-N2-N3-N4-N5-N6-N7-N8-N9-N10-N11-N12-N13-N14-N15-N16-N17-N18-N19-N20-N21-N22-N23- N24-N25-N26-N27(Formula XIV) and the identities of N1-N27 are as provided in Table 15; wherein Formula XV is represented as: O1-O2-O3-O4-O5-O6-O7-O8-O9-O10-O11-O12-O13-O14-O15-O16-O17-O18-O19-O20-O21-O22-O23- O24-O25-O26-O27-O28(Formula XV) and the identities of O1-O28are as provided in Table 16; wherein Formula XVI is represented as: P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-P15-P16-P17-P18-P19-P20-P21-P22-P23-P24-P25-P26- P27-P28-P29(Formula XVI) and the identities of P1-P29are as provided in Table 17; wherein Formula XVII is represented as: Q1-Q2-Q3-Q4-Q5-Q6-Q7-Q8-Q9-Q10-Q11-Q12-Q13-Q14-Q15-Q16-Q17-Q18-Q19-Q20-Q21-Q22-Q23- Q24-Q25-Q26-Q27-Q28-Q29-Q30(Formula XVII) and the identities of Q1-Q30are as provided in Table 18; wherein Formula XVIII is represented as: R1-R2-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-R17-R18-R19-R20-R21-R22-R23-R24- R25-R26-R27-R28-R29-R30-R31(Formula XVIII) and the identities of R1-R31are as provided in Table 19; ACTIVE / 131743364.1 3Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT wherein Formula XIX is represented as: S1-S2-S3-S4-S5-S6-S7-S8-S9-S10-S11-S12-S13-S14-S15-S16-S17-S18-S19-S20-S21-S22-S23-S24-S25-S26- S27-S28-S29-S30-S31-S32(Formula XIX) and the identities of S1-S32are as provided in Table 20; wherein Formula XX is represented as: T1-T2-T3-T4-T5-T6-T7-T8-T9-T10-T11-T12-T13-T14-T15-T16-T17-T18-T19-T20-T21-T22-T23-T24-T25- T26-T27-T28-T29-T30-T31-T32-T33(Formula XX) and the identities of T1-T33 are as provided in Table 21; wherein Formula XXI is represented as: U1-U2-U3-U4-U5-U6-U7-U8-U9-U10-U11-U12-U13-U14-U15-U16-U17-U18-U19-U20-U21-U22-U23- U24-U25-U26-U27-U28-U29-U30-U31-U32-U33-U34(Formula XXI) and the identities of U1-U34are as provided in Table 22; wherein Formula XXII is represented as: V1-V2-V3-V4-V5-V6-V7-V8-V9-V10-V11-V12-V13-V14-V15-V16-V17-V18-V19-V20-V21-V22-V23- V24-V25-V26-V27-V28-V29-V30-V31-V32-V33-V34-V35(Formula XXII) and the identities of V1-V35are as provided in Table 23; wherein Formula XXIII is represented as: W1-W2-W3-W4-W5-W6-W7-W8-W9-W10-W11-W12-W13-W14-W15-W16-W17-W18-W19-W20- W21-W22-W23-W24-W25-W26-W27-W28-W29-W30-W31-W32-W33-W34-W35-W36(Formula XXIII) and the identities of W1-W36are as provided in Table 24; wherein Formula XXIV is represented as: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-X23- X24-X25-X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37(Formula XXIV) and the identities of X1-X37are as provided in Table 25; wherein Formula XXV is represented as: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15-Y16-Y17-Y18-Y19-Y20-Y21-Y22-Y23- Y24-Y25-Y26-Y27-Y28-Y29-Y30-Y31-Y32-Y33-Y34-Y35-Y36-Y37-Y38 (Formula XXV) and the identities of Y1-Y38are as provided in Table 26; wherein Formula XXVI is represented as: Z1-Z2-Z3-Z4-Z5-Z6-Z7-Z8-Z9-Z10-Z11-Z12-Z13-Z14-Z15-Z16-Z17-Z18-Z19-Z20-Z21-Z22-Z23-Z24-Z25- Z26-Z27-Z28-Z29-Z30-Z31-Z32-Z33-Z34-Z35-Z36-Z37-Z38-Z39(Formula XXVI) and the identities of Z1-Z39are as provided in Table 27; wherein Formula XXVII is represented as: ACTIVE / 131743364.1 4Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT (AA)1-(AA)2-(AA)3-(AA)4-(AA)5-(AA)6-(AA)7-(AA)8-(AA)9-(AA)10-(AA)11-(AA)12-(AA)13- (AA)14-(AA)15-(AA)16-(AA)17-(AA)18-(AA)19-(AA)20-(AA)21-(AA)22-(AA)23-(AA)24-(AA)25- (AA)26-(AA)27-(AA)28-(AA)29-(AA)30-(AA)31-(AA)32-(AA)33-(AA)34-(AA)35-(AA)36-(AA)37- (AA)38-(AA)39-(AA)40-(AA)41(Formula XXVII) and the identities of (AA)1-(AA)41are as provided in Table 28; wherein Formula XXVIII is represented as: (BB)1-(BB)2-(BB)3-(BB)4-(BB)5-(BB)6-(BB)7-(BB)8-(BB)9-(BB)10-(BB)11-(BB)12-(BB)13- (BB)14-(BB)15-(BB)16-(BB)17-(BB)18-(BB)19-(BB)20-(BB)21-(BB)22-(BB)23-(BB)24-(BB)25- (BB)26-(BB)27-(BB)28-(BB)29-(BB)30-(BB)31-(BB)32-(BB)33-(BB)34-(BB)35-(BB)36-(BB)37- (BB)38-(BB)39-(BB)40-(BB)41-(BB)42-(BB)43(Formula XXVIII) and the identities of (BB)1-(BB)43are as provided in Table 29; wherein Formula XXIX is represented as: (CC)1-(CC)2-(CC)3-(CC)4-(CC)5-(CC)6-(CC)7-(CC)8-(CC)9-(CC)10-(CC)11-(CC)12-(CC)13- (CC)14-(CC)15-(CC)16-(CC)17-(CC)18-(CC)19-(CC)20-(CC)21-(CC)22-(CC)23-(CC)24-(CC)25- (CC)26-(CC)27-(CC)28-(CC)29-(CC)30-(CC)31-(CC)32-(CC)33-(CC)34-(CC)35-(CC)36-(CC)37- (CC)38-(CC)39-(CC)40-(CC)41-(CC)42-(CC)43-(CC)44-(CC)45-(CC)46-(CC)47(Formula XXIX) and the identities of (CC)1-(CC)47are as provided in Table 30; wherein Formula XXX is represented as: (DD)1-(DD)2-(DD)3-(DD)4-(DD)5-(DD)6-(DD)7-(DD)8-(DD)9-(DD)10-(DD)11-(DD)12-(DD)13- (DD)14-(DD)15-(DD)16-(DD)17-(DD)18-(DD)19-(DD)20-(DD)21-(DD)22-(DD)23-(DD)24-(DD)25- (DD)26-(DD)27-(DD)28-(DD)29-(DD)30-(DD)31-(DD)32-(DD)33-(DD)34-(DD)35-(DD)36-(DD)37- (DD)38-(DD)39-(DD)40-(DD)41-(DD)42-(DD)43-(DD)44-(DD)45-(DD)46-(DD)47-(DD)48(Formula XXX) and the identities of (DD)1-(DD)48are as provided in Table 31; wherein Formula XXXI is represented as: (EE)1-(EE)2-(EE)3-(EE)4-(EE)5-(EE)6-(EE)7-(EE)8-(EE)9-(EE)10-(EE)11-(EE)12-(EE)13-(EE)14- (EE)15-(EE)16-(EE)17-(EE)18-(EE)19-(EE)20-(EE)21-(EE)22-(EE)23-(EE)24-(EE)25-(EE)26-(EE)27- (EE)28-(EE)29-(EE)30-(EE)31-(EE)32-(EE)33-(EE)34-(EE)35-(EE)36-(EE)37-(EE)38-(EE)39-(EE)40- (EE)41-(EE)42-(EE)43-(EE)44-(EE)45-(EE)46-(EE)47-(EE)48-(EE)49(Formula XXXI) and the identities of (EE)1-(EE)49are as provided in Table 32; wherein Formula XXXII is represented as: (FF)1-(FF)2-(FF)3-(FF)4-(FF)5-(FF)6-(FF)7-(FF)8-(FF)9-(FF)10-(FF)11-(FF)12-(FF)13-(FF)14- (FF)15-(FF)16-(FF)17-(FF)18-(FF)19-(FF)20-(FF)21-(FF)22-(FF)23-(FF)24-(FF)25-(FF)26-(FF)27- ACTIVE / 131743364.1 5Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT (FF)28-(FF)29-(FF)30-(FF)31-(FF)32-(FF)33-(FF)34-(FF)35-(FF)36-(FF)37-(FF)38-(FF)39-(FF)40- (FF)41-(FF)42-(FF)43-(FF)44-(FF)45-(FF)46-(FF)47-(FF)48-(FF)49-(FF)50(Formula XXXII) and the identities of (FF)1-(FF)50are as provided in Table 33; and wherein Formula XXXIII is represented as: (GG)1-(GG)2-(GG)3-(GG)4-(GG)5-(GG)6-(GG)7-(GG)8-(GG)9-(GG)10-(GG)11-(GG)12-(GG)13- (GG)14-(GG)15-(GG)16-(GG)17-(GG)18-(GG)19-(GG)20-(GG)21-(GG)22-(GG)23-(GG)24-(GG)25- (GG)26-(GG)27-(GG)28-(GG)29-(GG)30-(GG)31-(GG)32-(GG)33-(GG)34-(GG)35-(GG)36-(GG)37- (GG)38-(GG)39-(GG)40-(GG)41-(GG)42-(GG)43-(GG)44-(GG)45-(GG)46-(GG)47-(GG)48-(GG)49- (GG)50-(GG)51(Formula XXXIII) and the identities of (GG)1-(GG)51are as provided in Table 34.

[0007] In some embodiments, the signal peptide comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 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, or 33.

[0008] In some embodiments, a signal peptide is provided, the signal peptide comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 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, or 33.

[0009] In some embodiments, a signal peptide as provided for herein is a novel signal peptide.

[0010] In some embodiments, a recombinant polypeptide is provided. In some embodiments, the recombinant polypeptide comprises a formula of X1-(Y1)a-Z1, wherein X1is a signal peptide, Y1is a peptide linker, and Z1is a payload protein, wherein a is an integer selected from 0 and 1.

[0011] In some embodiments, the signal peptide X1comprises an amino acid sequence selected from the group consisting of Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX. XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, or XXXIII; wherein Formula I is represented as: A1-A2-A3-A4-A5(Formula I) and the identities of A1-A5are as provided in Table 2; wherein Formula II is represented as: B1-B2-B3-B4-B5-B6-B7-B8-B9-B10-B11-B12-B13-B14-B15(Formula II) ACTIVE / 131743364.1 6Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT and the identities of B1-B15are as provided in Table 3; wherein Formula III is represented as: C1-C2-C3-C4-C5-C6-C7-C8-C9-C10-C11-C12-C13-C14-C15-C16(Formula III) and the identities of C1-C16are as provided in Table 4; wherein Formula IV is represented as: D1-D2-D3-D4-D5-D6-D7-D8-D9-D10-D11-D12-D13-D14-D15-D16-D17(Formula IV) and the identities of D1-D17are as provided in Table 5; wherein Formula V is represented as: E1-E2-E3-E4-E5-E6-E7-E8-E9-E10-E11-E12-E13-E14-E15-E16-E17-E18(Formula V) and the identities of E1-E18are as provided in Table 6; wherein Formula VI is represented as: F1-F2-F3-F4-F5-F6-F7-F8-F9-F10-F11-F12-F13-F14-F15-F16-F17-F18-F19(Formula VI) and the identities of F1-F19are as provided in Table 7; wherein Formula VII is represented as: G1-G2-G3-G4-G5-G6-G7-G8-G9-G10-G11-G12-G13-G14-G15-G16-G17-G18-G19-G20(Formula VII) and the identities of G1-G20are as provided in Table 8; wherein Formula VIII is represented as: H1-H2-H3-H4-H5-H6-H7-H8-H9-H10-H11-H12-H13-H14-H15-H16-H17-H18-H19-H20-H21 (Formula VIII) and the identities of H1-H21are as provided in Table 9; wherein Formula IX is represented as: I1-I2-I3-I4-I5-I6-I7-I8-I9-I10-I11-I12-I13-I14-I15-I16-I17-I18-I19-I20-I21-I22(Formula IX) and the identities of I1-I22are as provided in Table 10; wherein Formula X is represented as: J1-J2-J3-J4-J5-J6-J7-J8-J9-J10-J11-J12-J13-J14-J15-J16-J17-J18-J19-J20-J21-J22-J23(Formula X) and the identities of J1-J23are as provided in Table 11; wherein Formula XI is represented as: K1-K2-K3-K4-K5-K6-K7-K8-K9-K10-K11-K12-K13-K14-K15-K16-K17-K18-K19-K20-K21-K22-K23- K24(Formula XI) and the identities of K1-K24are as provided in Table 12; wherein Formula XII is represented as: L1-L2-L3-L4-L5-L6-L7-L8-L9-L10-L11-L12-L13-L14-L15-L16-L17-L18-L19-L20-L21-L22-L23-L24-L25(Formula XII) and the identities of L1-L25are as provided in Table 13; ACTIVE / 131743364.1 7Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT wherein Formula XIII is represented as: M1-M2-M3-M4-M5-M6-M7-M8-M9-M10-M11-M12-M13-M14-M15-M16-M17-M18-M19-M20-M21- M22-M23-M24-M25-M26(Formula XIII) and the identities of M1-M26are as provided in Table 14; wherein Formula XIV is represented as: N1-N2-N3-N4-N5-N6-N7-N8-N9-N10-N11-N12-N13-N14-N15-N16-N17-N18-N19-N20-N21-N22-N23- N24-N25-N26-N27(Formula XIV) and the identities of N1-N27 are as provided in Table 15; wherein Formula XV is represented as: O1-O2-O3-O4-O5-O6-O7-O8-O9-O10-O11-O12-O13-O14-O15-O16-O17-O18-O19-O20-O21-O22-O23- O24-O25-O26-O27-O28(Formula XV) and the identities of O1-O28are as provided in Table 16; wherein Formula XVI is represented as: P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-P15-P16-P17-P18-P19-P20-P21-P22-P23-P24-P25-P26- P27-P28-P29(Formula XVI) and the identities of P1-P29are as provided in Table 17; wherein Formula XVII is represented as: Q1-Q2-Q3-Q4-Q5-Q6-Q7-Q8-Q9-Q10-Q11-Q12-Q13-Q14-Q15-Q16-Q17-Q18-Q19-Q20-Q21-Q22-Q23- Q24-Q25-Q26-Q27-Q28-Q29-Q30(Formula XVII) and the identities of Q1-Q30are as provided in Table 18; wherein Formula XVIII is represented as: R1-R2-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-R17-R18-R19-R20-R21-R22-R23-R24- R25-R26-R27-R28-R29-R30-R31(Formula XVIII) and the identities of R1-R31are as provided in Table 19; wherein Formula XIX is represented as: S1-S2-S3-S4-S5-S6-S7-S8-S9-S10-S11-S12-S13-S14-S15-S16-S17-S18-S19-S20-S21-S22-S23-S24-S25-S26- S27-S28-S29-S30-S31-S32(Formula XIX) and the identities of S1-S32 are as provided in Table 20; wherein Formula XX is represented as: T1-T2-T3-T4-T5-T6-T7-T8-T9-T10-T11-T12-T13-T14-T15-T16-T17-T18-T19-T20-T21-T22-T23-T24-T25- T26-T27-T28-T29-T30-T31-T32-T33(Formula XX) and the identities of T1-T33are as provided in Table 21; wherein Formula XXI is represented as: ACTIVE / 131743364.1 8Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT U1-U2-U3-U4-U5-U6-U7-U8-U9-U10-U11-U12-U13-U14-U15-U16-U17-U18-U19-U20-U21-U22-U23- U24-U25-U26-U27-U28-U29-U30-U31-U32-U33-U34(Formula XXI) and the identities of U1-U34are as provided in Table 22; wherein Formula XXII is represented as: V1-V2-V3-V4-V5-V6-V7-V8-V9-V10-V11-V12-V13-V14-V15-V16-V17-V18-V19-V20-V21-V22-V23- V24-V25-V26-V27-V28-V29-V30-V31-V32-V33-V34-V35(Formula XXII) and the identities of V1-V35are as provided in Table 23; wherein Formula XXIII is represented as: W1-W2-W3-W4-W5-W6-W7-W8-W9-W10-W11-W12-W13-W14-W15-W16-W17-W18-W19-W20- W21-W22-W23-W24-W25-W26-W27-W28-W29-W30-W31-W32-W33-W34-W35-W36(Formula XXIII) and the identities of W1-W36are as provided in Table 24; wherein Formula XXIV is represented as: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-X23- X24-X25-X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37(Formula XXIV) and the identities of X1-X37are as provided in Table 25; wherein Formula XXV is represented as: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15-Y16-Y17-Y18-Y19-Y20-Y21-Y22-Y23- Y24-Y25-Y26-Y27-Y28-Y29-Y30-Y31-Y32-Y33-Y34-Y35-Y36-Y37-Y38(Formula XXV) and the identities of Y1-Y38are as provided in Table 26; wherein Formula XXVI is represented as: Z1-Z2-Z3-Z4-Z5-Z6-Z7-Z8-Z9-Z10-Z11-Z12-Z13-Z14-Z15-Z16-Z17-Z18-Z19-Z20-Z21-Z22-Z23-Z24-Z25- Z26-Z27-Z28-Z29-Z30-Z31-Z32-Z33-Z34-Z35-Z36-Z37-Z38-Z39(Formula XXVI) and the identities of Z1-Z39are as provided in Table 27; wherein Formula XXVII is represented as: (AA)1-(AA)2-(AA)3-(AA)4-(AA)5-(AA)6-(AA)7-(AA)8-(AA)9-(AA)10-(AA)11-(AA)12-(AA)13- (AA)14-(AA)15-(AA)16-(AA)17-(AA)18-(AA)19-(AA)20-(AA)21-(AA)22-(AA)23-(AA)24-(AA)25- (AA)26-(AA)27-(AA)28-(AA)29-(AA)30-(AA)31-(AA)32-(AA)33-(AA)34-(AA)35-(AA)36-(AA)37- (AA)38-(AA)39-(AA)40-(AA)41(Formula XXVII) and the identities of (AA)1-(AA)41are as provided in Table 28; wherein Formula XXVIII is represented as: (BB)1-(BB)2-(BB)3-(BB)4-(BB)5-(BB)6-(BB)7-(BB)8-(BB)9-(BB)10-(BB)11-(BB)12-(BB)13- (BB)14-(BB)15-(BB)16-(BB)17-(BB)18-(BB)19-(BB)20-(BB)21-(BB)22-(BB)23-(BB)24-(BB)25- ACTIVE / 131743364.1 9Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT (BB)26-(BB)27-(BB)28-(BB)29-(BB)30-(BB)31-(BB)32-(BB)33-(BB)34-(BB)35-(BB)36-(BB)37- (BB)38-(BB)39-(BB)40-(BB)41-(BB)42-(BB)43(Formula XXVIII) and the identities of (BB)1-(BB)43are as provided in Table 29; wherein Formula XXIX is represented as: (CC)1-(CC)2-(CC)3-(CC)4-(CC)5-(CC)6-(CC)7-(CC)8-(CC)9-(CC)10-(CC)11-(CC)12-(CC)13- (CC)14-(CC)15-(CC)16-(CC)17-(CC)18-(CC)19-(CC)20-(CC)21-(CC)22-(CC)23-(CC)24-(CC)25- (CC)26-(CC)27-(CC)28-(CC)29-(CC)30-(CC)31-(CC)32-(CC)33-(CC)34-(CC)35-(CC)36-(CC)37- (CC)38-(CC)39-(CC)40-(CC)41-(CC)42-(CC)43-(CC)44-(CC)45-(CC)46-(CC)47 (Formula XXIX) and the identities of (CC)1-(CC)47are as provided in Table 30; wherein Formula XXX is represented as: (DD)1-(DD)2-(DD)3-(DD)4-(DD)5-(DD)6-(DD)7-(DD)8-(DD)9-(DD)10-(DD)11-(DD)12-(DD)13- (DD)14-(DD)15-(DD)16-(DD)17-(DD)18-(DD)19-(DD)20-(DD)21-(DD)22-(DD)23-(DD)24-(DD)25- (DD)26-(DD)27-(DD)28-(DD)29-(DD)30-(DD)31-(DD)32-(DD)33-(DD)34-(DD)35-(DD)36-(DD)37- (DD)38-(DD)39-(DD)40-(DD)41-(DD)42-(DD)43-(DD)44-(DD)45-(DD)46-(DD)47-(DD)48(Formula XXX) and the identities of (DD)1-(DD)48are as provided in Table 31; wherein Formula XXXI is represented as: (EE)1-(EE)2-(EE)3-(EE)4-(EE)5-(EE)6-(EE)7-(EE)8-(EE)9-(EE)10-(EE)11-(EE)12-(EE)13-(EE)14- (EE)15-(EE)16-(EE)17-(EE)18-(EE)19-(EE)20-(EE)21-(EE)22-(EE)23-(EE)24-(EE)25-(EE)26-(EE)27- (EE)28-(EE)29-(EE)30-(EE)31-(EE)32-(EE)33-(EE)34-(EE)35-(EE)36-(EE)37-(EE)38-(EE)39-(EE)40- (EE)41-(EE)42-(EE)43-(EE)44-(EE)45-(EE)46-(EE)47-(EE)48-(EE)49(Formula XXXI) and the identities of (EE)1-(EE)49are as provided in Table 32; wherein Formula XXXII is represented as: (FF)1-(FF)2-(FF)3-(FF)4-(FF)5-(FF)6-(FF)7-(FF)8-(FF)9-(FF)10-(FF)11-(FF)12-(FF)13-(FF)14- (FF)15-(FF)16-(FF)17-(FF)18-(FF)19-(FF)20-(FF)21-(FF)22-(FF)23-(FF)24-(FF)25-(FF)26-(FF)27- (FF)28-(FF)29-(FF)30-(FF)31-(FF)32-(FF)33-(FF)34-(FF)35-(FF)36-(FF)37-(FF)38-(FF)39-(FF)40- (FF)41-(FF)42-(FF)43-(FF)44-(FF)45-(FF)46-(FF)47-(FF)48-(FF)49-(FF)50(Formula XXXII) and the identities of (FF)1-(FF)50 are as provided in Table 33; and wherein Formula XXXIII is represented as: (GG)1-(GG)2-(GG)3-(GG)4-(GG)5-(GG)6-(GG)7-(GG)8-(GG)9-(GG)10-(GG)11-(GG)12-(GG)13- (GG)14-(GG)15-(GG)16-(GG)17-(GG)18-(GG)19-(GG)20-(GG)21-(GG)22-(GG)23-(GG)24-(GG)25- (GG)26-(GG)27-(GG)28-(GG)29-(GG)30-(GG)31-(GG)32-(GG)33-(GG)34-(GG)35-(GG)36-(GG)37- (GG)38-(GG)39-(GG)40-(GG)41-(GG)42-(GG)43-(GG)44-(GG)45-(GG)46-(GG)47-(GG)48-(GG)49- (GG)50-(GG)51(Formula XXXIII) ACTIVE / 131743364.1 10Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT and the identities of (GG)1-(GG)51are as provided in Table 34.

[0012] In some embodiments, the signal peptide X1comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 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, or 33.

[0013] In some embodiments, the payload protein is a therapeutic peptide or protein.

[0014] In some embodiments, a nucleic acid molecule is provided. In some embodiments, the nucleic acid molecule encodes for a signal peptide as provided for herein.

[0015] In some embodiments, a nucleic acid molecule is provided. In some embodiments, the nucleic acid molecule encodes for a recombinant polypeptide as provided for herein.

[0016] In some embodiments, a vector is provided. In some embodiments, the vector comprises a nucleic acid molecule as provided for herein. In some embodiments, the nucleic acid molecule encodes for a signal peptide as provided for herein. In some embodiments, the nucleic acid molecule encodes for a recombinant polypeptide as provided for herein.

[0017] In some embodiments, a cell is provided. In some embodiments, the cell comprises a nucleic acid molecule as provided for herein. In some embodiments, the cell comprises a vector as provided for herein. In some embodiments, the nucleic acid molecule encodes for a signal peptide as provided for herein. In some embodiments, the nucleic acid molecule encodes for a recombinant polypeptide as provided for herein.

[0018] In some embodiments, a composition is provided. In some embodiments, the composition comprises a nucleic acid molecule as provided for herein. In some embodiments, the composition comprises a vector as provided for herein. In some embodiments, the nucleic acid molecule encodes for a signal peptide as provided for herein. In some embodiments, the nucleic acid molecule encodes for a recombinant polypeptide as provided for herein.

[0019] In some embodiments, a method for treating a disease or disorder in a subject in need thereof is provided. In some embodiments, the method comprises administering to the subject an effective among of a nucleic acid molecule as provided for herein to the subject, thereby treating the disease or disorder. In some embodiments, the nucleic acid molecule encodes for a recombinant polypeptide as provided for herein. In some embodiments, the disease or disorder is cancer.

[0020] In some embodiments, a method for treating cancer in a subject in need thereof is provided. In some embodiments, the method comprises administering to the subject a vector comprising a nucleic acid molecule encoding for a signal peptide fused or linked to a payload ACTIVE / 131743364.1 11Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT protein, wherein the signal peptide is a signal peptide as provided for herein and the payload protein is a therapeutic peptide or protein useful for the treatment of cancer. Brief Description of the Drawings

[0021] FIG. 1A provides a schematic of the construct comprising mCherry with the signal peptide at the N-terminus and its use for signal peptide screening by pDNA transfection in vitro.

[0022] FIG. 1B illustrates the quantification of mCherry signal assessment in the media of cells transfected with pDNA encoding mCherry with or without a signal peptide as provided for herein directly upstream of the mCherry sequence.

[0023] FIG. 1C illustrates the quantification of mCherry signal assessment in the media of cells transfected with pDNA encoding mCherry with or without a signal peptide as provided for herein directly upstream of the mCherry sequence.

[0024] FIG. 2A provides quantification of mCherry fluorescence in Hela cell lysates and medium at different time points. mCherry with no signal peptide was used as a control (“WT- mCherry”). gLuc, Gaussia luciferase.

[0025] FIG. 2B provides quantification of mCherry fluorescence in Hela cell lysate and medium after 72 hours.

[0026] FIG. 2C provides quantification of mCherry fluorescence in Huh7 cell lysates and medium at 72h after transfection.

[0027] FIG.3A provides quantification of time-dependent (100 ng mRNA per well) and dose dependent (at 72h) mCherry secretion in Huh7 cells, medium, and cell lysate.

[0028] FIG. 3B shows quantification of mCherry signal in different cell lines. Cells in 96- well plate were treated with mDLNPs-mRNA, at given time-points. Detailed Description

[0029] Before the present compositions and methods are described, it is to be understood that the scope of the disclosure is not limited to the particular processes, compositions, or methodologies described herein, as these may vary. It is also to be understood that the terminology used in the description is for the purpose of describing the particular versions or embodiments only, and is not intended to limit the scope of the present disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. It is further to be understood that any methods and materials similar or equivalent to those described herein can be used in the ACTIVE / 131743364.1 12Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT practice or testing of embodiments of the methods and systems disclosed herein, and such equivalents are within the scope of the present disclosure. Definitions

[0030] The following explanations of terms and methods are provided to better describe the present disclosure and to guide those of ordinary skill in the art in the practice of the present disclosure.

[0031] As used herein, “comprising” means “including” and the singular forms “a” or “an” or “the” include plural references unless the context clearly dictates otherwise. For example, reference to “comprising a therapeutic agent” includes one or a plurality of such therapeutic agents. The term “or” refers to a single element of stated alternative elements, unless the context clearly indicates otherwise. For example, the phrase “A or B” refers to A alone or B alone. The phrase “A, B, or a combination thereof” refers to A alone, B alone, or a combination of A and B. Similarly, “one or more of A and B” refers to A, B, or a combination of both A and B. The phrase “A and B” refers to a combination of A and B. Furthermore, the various elements, features and steps discussed herein, as well as other known equivalents for each such element, feature or step, can be mixed and matched by one of ordinary skill in this art to perform methods in accordance with principles described herein. Among the various elements, features, and steps some will be specifically included and others specifically excluded in particular examples.

[0032] In some examples, the numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth, used to describe and claim certain embodiments are to be understood as being modified in some instances by the term "about" or "approximately." For example, "about" or "approximately" can indicate + / - 10%, + / - 5%, or + / - 1% variation of the value it describes. Accordingly, in some embodiments, the numerical parameters set forth herein are approximations that can vary depending upon the desired properties for a particular embodiment. Additionally, where a phrase recites “about x to y,” the term “about” modifies both x and y and can be used interchangeably with the phrase “about x to about y” unless context dictates differently.

[0033] As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection (e.g., using commercially available reagents such as, for example, LIPOFECTIN® (Invitrogen Corp., San Diego, CA), LIPOFECTAMINE® (Invitrogen), ACTIVE / 131743364.1 13Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT FUGENE® (Roche Applied Science, Basel, Switzerland), JETPEI™ (Polyplus-transfection Inc., New York, NY), EFFECTENE® (Qiagen, Valencia, CA), DREAMFECT™ (OZ Biosciences, France) and the like), or electroporation (e.g., in vivo electroporation). Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (Molecular Cloning: A Laboratory Manual.2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.

[0034] Methods and materials of non-viral delivery of nucleic acids to cells further include biolistics, virosomes, liposomes, lipid nanoparticles, immunoliposomes, polycation or lipid- nucleic acid conjugates, naked DNA, artificial virions, and agent-enhanced uptake of DNA. Lipofection is described in U.S. Pat. Nos.5,049,386, 4,946,787; and 4,897,355 and lipofection reagents are sold commercially (e.g., TRANSFECTAM™ and LIPOFECTIN™). Cationic and neutral lipids that are suitable for efficient receptor-recognition lipofection of polynucleotides include those disclosed in WO91 / 17424 and WO 91 / 16024.

[0035] The chemical makeup of a peptide will be described herein by a series of amino acid single letter abbreviations or an “amino acid sequence / s” or “sequence / s,” which are conventional and known to those in the art. While reference sequences will be explicitly disclosed, in any aspect and embodiment, a reference sequence may be modified to include conservative amino acid substitutions, as well as variants and fragments, while maintaining the characteristics and functionality of the reference sequence.

[0036] As used herein, “payload protein” or “protein of interest” refers to the protein that will be generated by the host cell and subsequently exported from the cell due to the presence of the secretory signal peptide. Upon export, all, some, or none of the novel signal peptide may be fused to the payload protein. Optionally, a payload protein still being attached partially or fully to the novel signal peptide may be further processed, for example, to remove the remaining novel signal peptide. A payload protein may be any protein known or yet to be known, for example, an enzyme, enzyme inhibitor, growth factor, hormone, antibody, antigen, vaccine, a therapeutic agent, or any combination thereof. More specific examples follow herein below.

[0037] As used herein, the term “fused” or “linked” when used in reference to a protein having different domains or heterologous sequences means that the protein domains are part of the same peptide chain that are connected to one another with either peptide bonds or other covalent bonding. The domains or section can be linked or fused directly to one another or another domain or peptide sequence can be between the two domains or sequences and such sequences would still be considered to be fused or linked to one another. In some embodiments, ACTIVE / 131743364.1 14Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT the various domains or proteins provided for herein are linked or fused directly to one another or a linker sequences, such as the glycine / serine sequences described herein link the two domains together.

[0038] “Identity” as used herein refers to the subunit sequence identity between two polymeric molecules such as between two nucleic acid or amino acid molecules, such as, between two polynucleotide or polypeptide molecules. When two amino acid sequences have the same residues at the same positions; e.g., if a position in each of two polypeptide molecules is occupied by an Arginine, then they are identical at that position. The identity or extent to which two amino acid or two nucleic acid sequences have the same residues at the same positions in an alignment is often expressed as a percentage. The identity between two amino acid or two nucleic acid sequences is a direct function of the number of matching or identical positions; e.g., if half of the positions in two sequences are identical, the two sequences are 50% identical; if 90% of the positions (e.g., 9 of 10), are matched or identical, the two amino acids sequences are 90% identical.

[0039] By “substantially identical” is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In some embodiments, such a sequence is at least 60%, 80% or 85%, or 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison. Other percentages of identity in reference to specific sequences are described herein.

[0040] Sequence identity can be measured / determined using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis.53705, BLAST, BESTFIT, GAP, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, MUSCLE or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e3 and e100 indicating a closely related sequence. In some embodiments, sequence identity is determined by using BLAST with the default settings. In some embodiments, sequence identity is determined using Clustal Omega. ACTIVE / 131743364.1 15Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0041] To the extent embodiments provided for herein, includes composition comprising various proteins, these proteins may, in some instances, comprise amino acid sequences that have sequence identity to the amino acid sequences disclosed herein. Therefore, in certain embodiments, depending on the particular sequence, the degree of sequence identity is preferably greater than 50% (e.g., 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) to the SEQ ID NOs disclosed herein. In addition to these percentages, other percentages of identity are provided for herein. Identity between polypeptides can be determined by the Smith-Waterman homology search algorithm as implemented in the MPSRCH program (Oxford Molecular), using an affine gap search with parameters gap open penalty – 12 and gap extension penalty = 1.

[0042] These proteins may, compared to the disclosed proteins, include one or more (e.g., 1, 2, 3,4, 5, 6, 7, 8, 9, 10, etc.) conservative amino acid replacements i.e. replacements of one amino acid with another which has a related side chain. Genetically-encoded amino acids are generally divided into four families: (1) acidic i.e. aspartate, glutamate; (2) basic i.e. lysine, arginine, histidine; (3) non polar i.e. alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan; and (4) uncharged polar i.e. glycine, asparagine, glutamine, cysteine, serine, threonine, tyrosine. Phenylalanine, tryptophan, and tyrosine are sometimes classified jointly as aromatic amino acids. In general, Substitution of single amino acids within these families does not have a major effect on the biological activity. The proteins may have one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) single amino acid deletions relative to the disclosed protein sequences. The proteins may also include one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, etc.) insertions (e.g., each of 1, 2, 3, 4 or 5 amino acids) relative to the disclosed protein sequences.

[0043] “Encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA. ACTIVE / 131743364.1 16Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0044] As used herein, the following abbreviations for the commonly occurring nucleic acid bases are used: “A” refers to adenosine, “C” refers to cytosine, “G” refers to guanosine, “T” refers to thymidine, and “U” refers to uridine.

[0045] Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some versions contain an intron(s).

[0046] The term “oligonucleotide” typically refers to short polynucleotides. It will be understood that when a nucleotide sequence is represented by a DNA sequence (i.e., A, T, C, G), this also provides the corresponding RNA sequence (i.e., A, U, C, G) in which “U” replaces

[0047] The term “polynucleotide” as used herein is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Thus, the terms “nucleic acids” or “nucleic acid molecules” and “polynucleotides” as used herein are interchangeable. As used herein polynucleotides include, but are not limited to, all nucleic acid sequences which are obtained by any methods available in the art, including, without limitation, recombinant methods, i.e., the cloning of nucleic acid sequences from a recombinant library or a cell genome, using cloning technology and PCR, and the like, and by synthetic means.

[0048] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of a plurality of amino acid residues covalently linked by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.

[0049] As used herein, unless otherwise indicated, “antibody fragment” or “antigen binding fragment” refers to antigen binding fragments of antibodies, i.e. antibody fragments that retain the ability to bind specifically to the antigen bound by the full-length antibody, e.g., fragments that retain one or more CDR regions. Examples of antibody binding fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments; diabodies; linear antibodies; single- ACTIVE / 131743364.1 17Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT chain antibody molecules, e.g., sc-Fv; nanobodies (single domain antibody) and multispecific antibodies formed from antibody fragments.

[0050] A “Fab fragment” is comprised of one light chain and the CH1 and variable regions of one heavy chain. The heavy chain of a Fab molecule cannot form a disulfide bond with another heavy chain molecule.

[0051] An “Fc” region contains two heavy chain fragments comprising the CH2 and CH3 domains of an antibody. The two heavy chain fragments are held together by two or more disulfide bonds and by hydrophobic interactions of the CH3 domains.

[0052] A “Fab' fragment” contains one light chain and a portion or fragment of one heavy chain that contains the VHdomain and the CH1 domain and also the region between the CH1 and CH2 domains, such that an interchain disulfide bond can be formed between the two heavy chains of two Fab' fragments to form a F(ab')2molecule.

[0053] A “F(ab')2fragment” contains two light chains and two heavy chains containing a portion of the constant region between the CH1 and CH2 domains, such that an interchain disulfide bond is formed between the two heavy chains. A F(ab')2fragment thus is composed of two Fab' fragments that are held together by a disulfide bond between the two heavy chains.

[0054] The “Fv region” comprises the variable regions from both the heavy and light chains, but lacks the constant regions.

[0055] The term “single-chain Fv” or “scFv” antibody refers to antibody fragments comprising the VHand VLdomains of an antibody, wherein these domains are present in a single polypeptide chain. Generally, the Fv polypeptide further comprises a polypeptide linker between the VHand VLdomains which enables the scFv to form the desired structure for antigen binding. For a review of scFv, see Pluckthun (1994) THE PHARMACOLOGY OF MONOCLONAL ANTIBODIES, vol.113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315. See also, International Patent Application Publication No. WO 88 / 01649 and U.S. Pat. Nos.4,946, 778 and 5,260,203.

[0056] Antibody molecules can be monospecific (e.g., monovalent or bivalent), bispecific (e.g., bivalent, trivalent, tetravalent, pentavalent, or hexavalent), trispecific (e.g., trivalent, tetravalent, pentavalent, or hexavalent), or with higher orders of specificity (e.g, tetraspecific) and / or higher orders of valency beyond hexavalency. An antibody molecule can comprise a functional fragment of a light chain variable region and a functional fragment of a heavy chain variable region, or heavy and light chains may be fused together into a single polypeptide.

[0057] As used herein, the terms “comprising” (and any form of comprising, such as “comprise”, “comprises”, and “comprised”), “having” (and any form of having, such as “have” ACTIVE / 131743364.1 18Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT and “has”), “including” (and any form of including, such as “includes” and “include”), or “containing” (and any form of containing, such as “contains” and “contain”), are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. Any step or composition that uses the transitional phrase of “comprise” or “comprising” can also be said to describe the same with the transitional phase of “consisting of” or “consists.”

[0058] As used herein, the term “contacting” means bringing together of two elements in an in vitro system or an in vivo system. For example, “contacting” virus or vector described herein with an individual or patient or cell includes the administration of the virus to an individual or patient, such as a human, as well as, for example, introducing a compound into a sample containing a cellular or purified preparation containing the cell.

[0059] As used herein, the term “individual” or “subject,” or “patient” used interchangeably, means any animal, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans. In some embodiments, the subject is a human. A subject that is “in need thereof” refers to a subject that has been identified as requiring treatment for the condition that is to be treated and is treated with the specific intent of treating such condition. The conditions can be, for example, any of the conditions described herein.

[0060] The compositions disclosed herein may be provided to a subject in a variety of ways through administration of the composition to the subject. As used herein, administer or administration means to provide or the providing of a composition to a subject. Oral administration, as used herein, refers to delivery of an active agent through the mouth. Topical administration, as used herein, refers to the delivery of an active agent to a body surface, such as the skin, a mucosal membrane (e.g., nasal membrane, vaginal membrane, buccal membrane, or the like).

[0061] A “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal’s health continues to deteriorate. In contrast, a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal’s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal’s state of health.

[0062] “Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result or provides a therapeutic or prophylactic benefit. Such results may include, but are not limited to an amount that when ACTIVE / 131743364.1 19Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT administered to a mammal, causes a detectable level of immune cell activation compared to the immune cell activation detected in the absence of the composition. The immune response can be readily assessed by a plethora of art-recognized methods. The skilled artisan would understand that the amount of the composition administered herein varies and can be readily determined based on a number of factors such as the disease or condition being treated, the age and health and physical condition of the mammal being treated, the severity of the disease, the particular compound being administered, and the like.

[0063] Ranges: throughout this disclosure, various aspects of the embodiments can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. This applies regardless of the breadth of the range. Unless otherwise explicitly stated to the contrary, a range that is disclosed also includes the endpoints of the range. Novel Signal Peptides

[0064] Without being bound to any particular theory, the embodiments provided for herein have been found to show that novel signal peptides may direct payload proteins as provided for herein to be secreted from the cell. The payload proteins may or may not natively contain a signal peptide directing localization of said protein to the specific cellular compartment, e.g., secreted from the cell. Accordingly, the provided novel signal peptides can direct enhanced expression and secretion of a protein that natively contains a secretory signal peptide, or can direct secretion of a payload protein that does not natively contain a secretory signal peptide, e.g., a therapeutic protein, from the cell.

[0065] In some embodiments, a signal peptide is provided. In some embodiments, the signal peptide comprises an amino acid sequence as recited in Table 1 below: Table 1: Exemplary Novel Signal PeptidesACTIVE / 131743364.1 20Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENTACTIVE / 131743364.1 21Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0066] In some embodiments, the signal peptide comprises an amino acid sequence that is substantially similar to an amino acid sequence as recited in Table 1. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence as recited in Table 1. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 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, or 33. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 1. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 2. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 3. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 4. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 5. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 6. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 7. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) ACTIVE / 131743364.1 22Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT identical to an amino acid sequence of SEQ ID NO: 8. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 9. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 10. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 11. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 12. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 13. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 14. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 15. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 16. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 17. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 18. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an ACTIVE / 131743364.1 23Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid sequence of SEQ ID NO: 19. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 21. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 22. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 23. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 24. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 25. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 26. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 27. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 28. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 29. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an ACTIVE / 131743364.1 24Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid sequence of SEQ ID NO: 30. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 31. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 32. In some embodiments, the signal peptide comprises an amino acid sequence that is at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) identical to an amino acid sequence of SEQ ID NO: 33.

[0067] In some embodiments, the signal peptide is a variant of an amino acid sequence as provided in Table 1. In some embodiments, the signal peptide comprises an amino acid sequence as defined by Formula I-XXXIII below.

[0068] Variants of SEQ ID NO: 1 (Formula I)

[0069] In some embodiments, the signal peptide comprises an amino acid sequence represented by: A1-A2-A3-A4-A5(Formula I); wherein the identity of each of A1– A5are as provided for in Table 2 below. Table 2

[0070] In some embodiments, A1is methionine (M). In some embodiments, A2is amino acid selected from the group consisting of G and V. In some embodiments, A3 is amino acid selected from the group consisting of S and P. In some embodiments, A4 is serine (S). In some embodiments, A5is glycine (G).

[0071] It is to be understood that a variant of SEQ ID NO: 1 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one ACTIVE / 131743364.1 25Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution to be within the scope of Formula I. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 1 and a substitution at position 2 of SEQ ID NO: 1. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 1 and a substitution at position 3 of SEQ ID NO: 1. The variant may also comprise any number of substitutions as provided by Formula I. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 1 and a substitution at at least one position corresponding to position 2 or 3 of SEQ ID NO: 1. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 1 and a substitution at more than one position corresponding to position 2 or 3 of SEQ ID NO: 1.

[0072] Variants of SEQ ID NO: 2 (Formula II)

[0073] In some embodiments, the signal peptide comprises an amino acid sequence represented by: B1-B2-B3-B4-B5-B6-B7-B8-B9-B10-B11-B12-B13-B14-B15(Formula II); wherein the identity of each of B1– B15are as provided for in Table 3 below. Table 3ACTIVE / 131743364.1 26Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0074] In some embodiments, B1is methionine (M). In some embodiments, B2is an amino acid selected from the group consisting of K, L, N, and R. In some embodiments, B3is an amino acid selected from the group consisting of L, P, and V. In some embodiments, B4is an amino acid selected from the group consisting of L and F. In some embodiments, B5is an amino acid selected from the group consisting of L, V, and I. In some embodiments, B6is an amino acid selected from the group consisting of L and I. In some embodiments, B7is an amino acid selected from the group consisting of L and A. In some embodiments, B8is an amino acid selected from the group consisting of A, L, V, G, C, and F. In some embodiments, B9is an amino acid selected from the group consisting of L, F, T, and I. In some embodiments, B10is an amino acid selected from the group consisting of L and V. In some embodiments, B11is an amino acid selected from the group consisting of A, G, T, and L. In some embodiments, B12is an amino acid selected from the group consisting of L, A, and V. In some embodiments, B13is an amino acid selected from the group consisting of A, C, V, and S. In some embodiments, B14is an amino acid selected from the group consisting of L, A, W, and V. In some embodiments, B15is an amino acid selected from the group consisting of A and C.

[0075] It is to be understood that a variant of SEQ ID NO: 2 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula II. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 2 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 3 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 4 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 5 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 6 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 7 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 8 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 9 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 10 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 11 of SEQ ID NO: 2. In some embodiments, the signal peptide ACTIVE / 131743364.1 27Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 12 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 13 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 14 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at position 15 of SEQ ID NO: 2. The variant may also comprise any number of substitutions as provided by Formula II. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of SEQ ID NO: 2. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 2 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of SEQ ID NO: 2.

[0076] Variants of SEQ ID NO: 3 (Formula III)

[0077] In some embodiments, the signal peptide comprises an amino acid sequence represented by: C1-C2-C3-C4-C5-C6-C7-C8-C9-C10-C11-C12-C13-C14-C15-C16(Formula III); wherein the identity of each of C1 – C16 are as provided for in Table 4 below. Table 4ACTIVE / 131743364.1 28Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0078] In some embodiments, C1 is methionine (M). In some embodiments, C2 is an amino acid selected from the group consisting of L, K, and R. In some embodiments, C3 is an amino acid selected from the group consisting of L, T, V, and P. In some embodiments, C4is leucine (L). In some embodiments, C5is leucine (L). In some embodiments, C6is an amino acid selected from the group consisting of L, I, and V. In some embodiments, C7is an amino acid selected from the group consisting of L, V, and F. In some embodiments, C8is an amino acid selected from the group consisting of L, S, V, A. In some embodiments, C9is an amino acid selected from the group consisting of L, A, and C. In some embodiments, C10is leucine (L). In some embodiments, C11is an amino acid selected from the group consisting of L and V. In some embodiments, C12is an amino acid selected from the group consisting of G, A, and L. In some embodiments, C13 is an amino acid selected from the group consisting of L, A, S, and G. In some embodiments, C14 is an amino acid selected from the group consisting of A, S, T, and V. In some embodiments, C15is an amino acid selected from the group consisting of L, S, and W.. In some embodiments, C16is an amino acid selected from the group consisting of A and G.

[0079] It is to be understood that a variant of SEQ ID NO: 3 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula III. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 2 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 3 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 6 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 7 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 8 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 9 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of ACTIVE / 131743364.1 29Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT SEQ ID NO: 3 and a substitution at position 11 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 12 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 13 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 14 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 15 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at position 16 of SEQ ID NO: 3. The variant may also comprise any number of substitutions as provided by Formula III. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at at least one position corresponding to position 2, 3, 6, 7, 8, 9, 11, 12, 13, 14, 15, or 16 of SEQ ID NO: 3. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 3 and a substitution at more than one position corresponding to position 2, 3, 6, 7, 8, 9, 11, 12, 13, 14, 15, or 16 of SEQ ID NO: 3.

[0080] Variants of SEQ ID NO: 4 (Formula IV)

[0081] In some embodiments, the signal peptide comprises an amino acid sequence represented by: D1-D2-D3-D4-D5-D6-D7-D8-D9-D10-D11-D12-D13-D14-D15-D16-D17(Formula IV); wherein the identity of each of D1– D17are as provided for in Table 5 below. Table 5ACTIVE / 131743364.1 30Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0082] In some embodiments, D1is methionine (M). In some embodiments, D2is an amino acid selected from the group consisting of L, A, G, R, and W. In some embodiments, D3is an amino acid selected from the group consisting of L and A. In some embodiments, D4is an amino acid selected from the group consisting of L and F. In some embodiments, D5 is an amino acid selected from the group consisting of L, A, and V. In some embodiments, D6is an amino acid selected from the group consisting of L, V, I, and F. In some embodiments, D7is an amino acid selected from the group consisting of L and F. In some embodiments, D8is an amino acid selected from the group consisting of L and F. In some embodiments, D9is an amino acid selected from the group consisting of L and A. In some embodiments, D10is an amino acid selected from the group consisting of L, A, and S. In some embodiments, D11is an amino acid selected from the group consisting of L and F. In some embodiments, D12is an amino acid selected from the group consisting of L and A. In some embodiments, D13is an amino acid selected from the group consisting of A, G, L, and P. In some embodiments, D14is an amino acid selected from the group consisting of L, G, and A. In some embodiments, D15 is an amino acid selected from the group consisting of A, V, S, L, and T. In some embodiments, D16is an amino acid selected from the group consisting of L and Q. In some embodiments, D17is an amino acid selected from the group consisting of A and G.

[0083] It is to be understood that a variant of SEQ ID NO: 4 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula IV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 2 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 3 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a ACTIVE / 131743364.1 31Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution at position 4 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 5 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 6 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 7 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 8 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 9 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 10 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 11 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 12 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 13 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 14 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 15 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 16 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at position 17 of SEQ ID NO: 4. The variant may also comprise any number of substitutions as provided by Formula IV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 of SEQ ID NO: 4. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 4 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 of SEQ ID NO: 4.

[0084] Variants of SEQ ID NO: 5 (Formula V)

[0085] In some embodiments, the signal peptide comprises an amino acid sequence represented by: E1-E2-E3-E4-E5-E6-E7-E8-E9-E10-E11-E12-E13-E14-E15-E16-E17-E18(Formula V); wherein the identity of each of E1– E18are as provided for in Table 6 below. ACTIVE / 131743364.1 32Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT Table 6

[0086] In some embodiments, E1 is methionine (M). In some embodiments, E2 is an amino acid selected from the group consisting of K, L, A, and R. In some embodiments, E3is leucine (L). In some embodiments, E4is an amino acid selected from the group consisting of L and V. In some embodiments, E5is leucine (L). In some embodiments, E6is an amino acid selected from the group consisting of L and V. In some embodiments, E7is an amino acid selected from the group consisting of L, V, and F. In some embodiments, E8is an amino acid selected from the group consisting of L, I, and V. In some embodiments, E9is an amino acid selected from the group consisting of L and F. In some embodiments, E10is leucine (L). In some embodiments, E11is an amino acid selected from the group consisting of L, S, and A. In some embodiments, E12 is leucine (L). In some embodiments, E13 is an amino acid selected from the group consisting of L and V. In some embodiments, E14 is an amino acid selected from the group consisting of G, L, and S. In some embodiments, E15is an amino acid selected from the ACTIVE / 131743364.1 33Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT group consisting of L and G. In some embodiments, E16is an amino acid selected from the group consisting of V, A, T, and C. In some embodiments, E17is an amino acid selected from the group consisting of L, Q, and S. In some embodiments, E18is an amino acid selected from the group consisting of A, G, and S.

[0087] It is to be understood that a variant of SEQ ID NO: 5 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula V. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 2 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 4 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 6 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 7 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 8 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 9 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 11 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 13 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 14 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 15 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 16 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 17 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at position 18 of SEQ ID NO: 5. The variant may also comprise any number of substitutions as provided by Formula V. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at at least one position corresponding to position 2, 4, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, or 18 of SEQ ID NO: 5. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 5 and a substitution at more than one position corresponding to position 2, 4, 6, 7, 8, 9, 11, 13, 14, 15, 16, 17, or 18 of SEQ ID NO: 5. ACTIVE / 131743364.1 34Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0088] Variants of SEQ ID NO: 6 (Formula VI)

[0089] In some embodiments, the signal peptide comprises an amino acid sequence represented by: F1-F2-F3-F4-F5-F6-F7-F8-F9-F10-F11-F12-F13-F14-F15-F16-F17-F18-F19(Formula VI); wherein the identity of each of F1– F19are as provided for in Table 7 below. Table 7

[0090] In some embodiments, F1is methionine (M). In some embodiments, F2is an amino acid selected from the group consisting of A, K, R, and D. In some embodiments, F3is an amino acid selected from the group consisting of L, W, F, and A. In some embodiments, F4is an amino acid selected from the group consisting of L, T, A, and G. In some embodiments, F5is an amino acid selected from the group consisting of L and P. In some embodiments, F6 is ACTIVE / 131743364.1 35Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT an amino acid selected from the group consisting of L and S. In some embodiments, F7is an amino acid selected from the group consisting of L, A, and W. In some embodiments, F8is an amino acid selected from the group consisting of L, V, and A. In some embodiments, F9is an amino acid selected from the group consisting of L and F. In some embodiments, F10is leucine (L). In some embodiments, F11is an amino acid selected from the group consisting of L and V. In some embodiments, F12is an amino acid selected from the group consisting of L and A. In some embodiments, F13is an amino acid selected from the group consisting of L and V. In some embodiments, F14 is an amino acid selected from the group consisting of L, A, and C. In some embodiments, F15is an amino acid selected from the group consisting of T and A. In some embodiments, F16is an amino acid selected from the group consisting of G and L. In some embodiments, F17is an amino acid selected from the group consisting of V, A, and S. In some embodiments, F18is an amino acid selected from the group consisting of L, Q, and H. In some embodiments, F19is an amino acid selected from the group consisting of A, S, G, and C.

[0091] It is to be understood that a variant of SEQ ID NO: 6 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula VI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 2 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 3 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 4 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 5 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 6 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 7 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 8 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 9 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 11 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 12 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 13 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of ACTIVE / 131743364.1 36Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT SEQ ID NO: 6 and a substitution at position 14 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 15 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 16 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 17 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 18 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at position 19 of SEQ ID NO: 6. The variant may also comprise any number of substitutions as provided by Formula VI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, or 19 of SEQ ID NO: 6. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 6 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, or 19 of SEQ ID NO: 6.

[0092] Variants of SEQ ID NO: 7 (Formula VII)

[0093] In some embodiments, the signal peptide comprises an amino acid sequence represented by: G1-G2-G3-G4-G5-G6-G7-G8-G9-G10-G11-G12-G13-G14-G15-G16-G17-G18-G19-G20(Formula VII); wherein the identity of each of G1– G20are as provided for in Table 8 below. Table 8ACTIVE / 131743364.1 37Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0094] In some embodiments, G1is methionine (M). In some embodiments, G2is an amino acid selected from the group consisting of A and K. In some embodiments, G3is an amino acid selected from the group consisting of L, S, and P. In some embodiments, G4is an amino acid selected from the group consisting of L and P. In some embodiments, G5is an amino acid selected from the group consisting of L and A. In some embodiments, G6is leucine (L). In some embodiments, G7 is an amino acid selected from the group consisting of L and V. In some embodiments, G8 is an amino acid selected from the group consisting of L and A. In some embodiments, G9is leucine (L). In some embodiments, G10is an amino acid selected from the group consisting of L and V. In some embodiments, G11is leucine (L). In some embodiments, G12is an amino acid selected from the group consisting of L and A. In some embodiments, G13is leucine (L). In some embodiments, G14is an amino acid selected from the group consisting of L and A. In some embodiments, G15is an amino acid selected from the group consisting of L, V, and A. In some embodiments, G16is an amino acid selected from the group consisting of G, P, A, S, and L. In some embodiments, G17is an amino acid selected from the group consisting of G, V, L, and S. In some embodiments, G18is an amino acid selected from the group consisting of A, V, S, and T. In some embodiments, G19 is an amino acid selected from the group consisting of L and A. In some embodiments, G20 is an amino acid selected from the group consisting of A, G, and S.

[0095] It is to be understood that a variant of SEQ ID NO: 7 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one ACTIVE / 131743364.1 38Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution to be within the scope of Formula VII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 2 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 3 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 4 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 5 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 7 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 8 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 10 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 12 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 14 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 15 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 16 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 17 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 18 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 19 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at position 20 of SEQ ID NO: 7. The variant may also comprise any number of substitutions as provided by Formula VII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 7, 8, 10, 12, 14, 15, 16, 17, 18, 19, or 20 of SEQ ID NO: 7. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 7 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 7, 8, 10, 12, 14, 15, 16, 17, 18, 19, or 20 of SEQ ID NO: 7.

[0096] Variants of SEQ ID NO: 8 (Formula VIII)

[0097] In some embodiments, the signal peptide comprises an amino acid sequence represented by: ACTIVE / 131743364.1 39Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT H1-H2-H3-H4-H5-H6-H7-H8-H9-H10-H11-H12-H13-H14-H15-H16-H17-H18-H19-H20-H21(Formula VIII); wherein the identity of each of H1– H21are as provided for in Table 9 below. Table 9

[0098] In some embodiments, H1is methionine (M). In some embodiments, H2is an amino acid selected from the group consisting of A and K. In some embodiments, H3is an amino acid selected from the group consisting of L, P, A, and V. In some embodiments, H4is an amino acid selected from the group consisting of L and S. In some embodiments, H5is an amino acid selected from the group consisting of L and V. In some embodiments, H6is an ACTIVE / 131743364.1 40Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of L and A. In some embodiments, H7is leucine (L). In some embodiments, H8is an amino acid selected from the group consisting of L and A. In some embodiments, H9is an amino acid selected from the group consisting of L and A. In some embodiments, H10is an amino acid selected from the group consisting of L and V. In some embodiments, H11is leucine (L). In some embodiments, H12is an amino acid selected from the group consisting of L and V. In some embodiments, H13is an amino acid selected from the group consisting of L and A. In some embodiments, H14is an amino acid selected from the group consisting of L and A. In some embodiments, H15 is an amino acid selected from the group consisting of L, A, and C. In some embodiments, H16is an amino acid selected from the group consisting of L and A. In some embodiments, H17is an amino acid selected from the group consisting of L, A, and T. In some embodiments, H18is an amino acid selected from the group consisting of L and P. In some embodiments, H19is an amino acid selected from the group consisting of A, V, S, and G. In some embodiments, H20is an amino acid selected from the group consisting of Q and L. In some embodiments, H21is an amino acid selected from the group consisting of A, G, and S.

[0099] It is to be understood that a variant of SEQ ID NO: 8 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula VIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 2 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 3 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 4 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 5 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 6 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 8 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 9 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 10 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 12 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 13 of SEQ ID NO: 8. In some embodiments, the signal peptide ACTIVE / 131743364.1 41Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 14 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 15 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 16 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 17 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 18 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 19 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 20 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at position 21 of SEQ ID NO: 8. The variant may also comprise any number of substitutions as provided by Formula VIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of SEQ ID NO: 8. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 8 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 of SEQ ID NO: 8.

[0100] Variants of SEQ ID NO: 9 (Formula IX)

[0101] In some embodiments, the signal peptide comprises an amino acid sequence represented by: I1-I2-I3-I4-I5-I6-I7-I8-I9-I10-I11-I12-I13-I14-I15-I16-I17-I18-I19-I20-I21-I22(Formula IX); wherein the identity of each of I1– I22are as provided for in Table 10 below. Table 10ACTIVE / 131743364.1 42Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0102] In some embodiments, I1is methionine (M). In some embodiments, I2is an amino acid selected from the group consisting of R, A, K, and D. In some embodiments, I3is an amino acid selected from the group consisting of L and P. In some embodiments, I4is an amino acid selected from the group consisting of L, R, and A. In some embodiments, I5is an amino acid selected from the group consisting of V, R, and L. In some embodiments, I6is an amino acid selected from the group consisting of L, P, and A. In some embodiments, I7is an amino acid selected from the group consisting of L and A. In some embodiments, I8is an amino acid selected from the group consisting of L and Q. In some embodiments, I9is an amino acid selected from the group consisting of L and V. In some embodiments, I10is an amino acid selected from the group consisting of L and A. In some embodiments, I11 is an amino acid selected from the group consisting of L and G. In some embodiments, I12is leucine (L). In some embodiments, I13is leucine (L). In some embodiments, I14is an amino acid selected from the group consisting of L and A. In some embodiments, I15is an amino acid selected from the group consisting of L and A. In some embodiments, I16is an amino acid selected from the group consisting of L and A. In some embodiments, I17is an amino acid selected from the ACTIVE / 131743364.1 43Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT group consisting of L and A. In some embodiments, I18is an amino acid selected from the group consisting of P, L, A, and G. In some embodiments, I19is an amino acid selected from the group consisting of G, L, A, and P. In some embodiments, I20is an amino acid selected from the group consisting of A, V, G, and S. In some embodiments, I21is an amino acid selected from the group consisting of R, L, Q, and A. In some embodiments, I22is an amino acid selected from the group consisting of G, A, S, and C.

[0103] It is to be understood that a variant of SEQ ID NO: 9 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula IX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 2 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 3 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 4 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 5 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 6 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 7 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 8 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 9 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 10 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 11 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 14 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 15 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 16 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 17 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 18 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 19 of SEQ ACTIVE / 131743364.1 44Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 20 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 21 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at position 22 of SEQ ID NO: 9. The variant may also comprise any number of substitutions as provided by Formula IX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14, 15, 16, 17, 18, 19, 20, 21, or 22 of SEQ ID NO: 9. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 9 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 14, 15, 16, 17, 18, 19, 20, 21, or 22 of SEQ ID NO: 9.

[0104] Variants of SEQ ID NO: 10 (Formula X)

[0105] In some embodiments, the signal peptide comprises an amino acid sequence represented by: J1-J2-J3-J4-J5-J6-J7-J8-J9-J10-J11-J12-J13-J14-J15-J16-J17-J18-J19-J20-J21-J22-J23(Formula X); wherein the identity of each of J1 – J23 are as provided for in Table 11 below. Table 11ACTIVE / 131743364.1 45Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0106] In some embodiments, J1is methionine (M). In some embodiments, J2is an amino acid selected from the group consisting of K, A, and R. In some embodiments, J3is an amino acid selected from the group consisting of P, L, G, and S. In some embodiments, J4is serine (S). In some embodiments, J5is an amino acid selected from the group consisting of L and A. In some embodiments, J6is an amino acid selected from the group consisting of A and L. In some embodiments, J7 is an amino acid selected from the group consisting of L and A. In some embodiments, J8is leucine (L). In some embodiments, J9is an amino acid selected from the group consisting of L and A. In some embodiments, J10is an amino acid selected from the group consisting of L and V. In some embodiments, J11is an amino acid selected from the group consisting of L and A. In some embodiments, J12is leucine (L). In some embodiments, J13is an amino acid selected from the group consisting of L, V, and A. In some embodiments, J14is an amino acid selected from the group consisting of L and A. In some embodiments, J15is an amino acid selected from the group consisting of L and A. In some embodiments, J16is an amino acid selected from the group consisting of L and A. In some embodiments, J17is an amino acid selected from the group consisting of L and F. In some embodiments, J18is an amino acid selected from the group consisting of L, A, and S. In some embodiments, J19 is an amino acid selected from the group consisting of S, P, and G. In some embodiments, J20is an amino acid selected from the group consisting of L, A, and P. In some embodiments, J21is an amino acid selected from the group consisting of A, V, S, and G. In some embodiments, J22is an amino acid selected from the group consisting of L and S. In some embodiments, J23is an amino acid selected from the group consisting of A, G, and S. ACTIVE / 131743364.1 46Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0107] It is to be understood that a variant of SEQ ID NO: 10 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula X. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 2 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 3 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 5 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 6 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 7 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 9 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 10 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 11 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 13 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 14 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 15 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 16 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 17 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 18 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 19 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 20 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 21 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 22 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at position 23 of SEQ ID NO: 10. The variant may also comprise any number of substitutions as provided by Formula ACTIVE / 131743364.1 47Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT X. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at at least one position corresponding to position 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 of SEQ ID NO: 10. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 10 and a substitution at more than one position corresponding to position 2, 3, 5, 6, 7, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 of SEQ ID NO: 10.

[0108] Variants of SEQ ID NO: 11 (Formula XI)

[0109] In some embodiments, the signal peptide comprises an amino acid sequence represented by: K1-K2-K3-K4-K5-K6-K7-K8-K9-K10-K11-K12-K13-K14-K15-K16-K17-K18-K19-K20-K21-K22-K23- K24(Formula XI); wherein the identity of each of K1– K24are as provided for in Table 12 below. Table 12ACTIVE / 131743364.1 48Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0110] In some embodiments, K1is methionine (M). In some embodiments, K2is an amino acid selected from the group consisting of A and R. In some embodiments, K3is an amino acid selected from the group consisting of R, P, L, and S. In some embodiments, K4 is an amino acid selected from the group consisting of A, S, P, and L. In some embodiments, K5 is an amino acid selected from the group consisting of S, R, and G. In some embodiments, K6is an amino acid selected from the group consisting of L and G. In some embodiments, K7is an amino acid selected from the group consisting of L and A. In some embodiments, K8is an amino acid selected from the group consisting of L, A, and S. In some embodiments, K9is an amino acid selected from the group consisting of L and A. In some embodiments, K10is an amino acid selected from the group consisting of L, A, G, and V. In some embodiments, K11is an amino acid selected from the group consisting of L and A. In some embodiments, K12is an amino acid selected from the group consisting of L and A. In some embodiments, K13is an amino acid selected from the group consisting of L, A, and V. In some embodiments, K14 is an amino acid selected from the group consisting of L and A. In some embodiments, K15 is leucine (L). In some embodiments, K16is an amino acid selected from the group consisting of L and A. In some embodiments, K17is an amino acid selected from the group consisting of L and A. In some embodiments, K18is an amino acid selected from the group consisting of L and A. In some embodiments, K19is an amino acid selected from the group consisting of L, A, and P. In some embodiments, K20is an amino acid selected from the group consisting of P, G, and S. In some embodiments, K21is an amino acid selected from the group consisting of P, G, L, and V. In some embodiments, K22is an amino acid selected from the group consisting of V, S, A, T, and G. In some embodiments, K23is an amino acid selected from the group consisting of L, R, and E. In some embodiments, K24 is an amino acid selected from the group consisting of A, G, and S. ACTIVE / 131743364.1 49Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0111] It is to be understood that a variant of SEQ ID NO: 11 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 2 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 3 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 4 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 5 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 6 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 7 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 8 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 9 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 10 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 11 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 12 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 13 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 14 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 16 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 17 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 18 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 19 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 20 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 21 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of ACTIVE / 131743364.1 50Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT SEQ ID NO: 11 and a substitution at position 22 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 23 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at position 24 of SEQ ID NO: 11. The variant may also comprise any number of substitutions as provided by Formula XI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, or 24 of SEQ ID NO: 11. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 11 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, or 24 of SEQ ID NO: 11.

[0112] Variants of SEQ ID NO: 12 (Formula XII)

[0113] In some embodiments, the signal peptide comprises an amino acid sequence represented by: L1-L2-L3-L4-L5-L6-L7-L8-L9-L10-L11-L12-L13-L14-L15-L16-L17-L18-L19-L20-L21-L22-L23-L24-L25(Formula XII); wherein the identity of each of L1 – L25 are as provided for in Table 13 below. Table 13ACTIVE / 131743364.1 51Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0114] In some embodiments, L1is methionine (M). In some embodiments, L2is an amino acid selected from the group consisting of A, G, and R. In some embodiments, L3is an amino acid selected from the group consisting of S, L, R, and P. In some embodiments, L4is an amino acid selected from the group consisting of L, A, R, P, and S. In some embodiments, L5is an amino acid selected from the group consisting of L, G, and R. In some embodiments, L6is an amino acid selected from the group consisting of L and R. In some embodiments, L7is an amino acid selected from the group consisting of A, L, and S. In some embodiments, L8 is an amino acid selected from the group consisting of L and P. In some embodiments, L9 is leucine (L). In some embodiments, L10is an amino acid selected from the group consisting of L and S. In some embodiments, L11is an amino acid selected from the group consisting of L, A, and V. In some embodiments, L12is an amino acid selected from the group consisting of L and V. In some embodiments, L13is leucine (L). In some embodiments, L14is an amino acid selected from the group consisting of L, F, and V. In some embodiments, L15is leucine (L). In some embodiments, L16is an amino acid selected from the group consisting of L and A. In some embodiments, L17is an amino acid selected from the group consisting of L and G. In some embodiments, L18is an amino acid selected from the group consisting of L and V. In some embodiments, L19 is an amino acid selected from the group consisting of L, A, and F. In some embodiments, L20 is an amino acid selected from the group consisting of L and P. In some embodiments, L21is an amino acid selected from the group consisting of P, G, S, and L. In ACTIVE / 131743364.1 52Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT some embodiments, L22is an amino acid selected from the group consisting of G, S, V, and L. In some embodiments, L23is an amino acid selected from the group consisting of A, V, S, and T. In some embodiments, L24is an amino acid selected from the group consisting of L, S, H, and Q. In some embodiments, L25is an amino acid selected from the group consisting of A, G, and S.

[0115] It is to be understood that a variant of SEQ ID NO: 12 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 2 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 3 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 4 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 5 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 6 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 7 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 8 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 10 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 11 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 12 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 14 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 16 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 17 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 18 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 19 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 20 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino ACTIVE / 131743364.1 53Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT acid sequence of SEQ ID NO: 12 and a substitution at position 21 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 22 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 23 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 24 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at position 25 of SEQ ID NO: 12. The variant may also comprise any number of substitutions as provided by Formula XII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 of SEQ ID NO: 12. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 12 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 of SEQ ID NO: 12.

[0116] Variants of SEQ ID NO: 13 (Formula XIII)

[0117] In some embodiments, the signal peptide comprises an amino acid sequence represented by: M1-M2-M3-M4-M5-M6-M7-M8-M9-M10-M11-M12-M13-M14-M15-M16-M17-M18-M19-M20-M21- M22-M23-M24-M25-M26(Formula XIII); wherein the identity of each of M1– M26are as provided for in Table 14 below. Table 14ACTIVE / 131743364.1 54Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0118] In some embodiments, M1 is methionine (M). In some embodiments, M2 is an amino acid selected from the group consisting of A, L, and R. In some embodiments, M3is an amino acid selected from the group consisting of A, P, L, and G. In some embodiments, M4is an amino acid selected from the group consisting of L, A, P, R, G, and S. In some embodiments, M5is an amino acid selected from the group consisting of S, L, and R. In some embodiments, M6is an amino acid selected from the group consisting of R, A, and L. In some embodiments, M7is an amino acid selected from the group consisting of L, T, P, S, and A. In some embodiments, M8is an amino acid selected from the group consisting of P, A, S, and L. In some embodiments, M9is an amino acid selected from the group consisting of L and A. In some embodiments, M10 is an amino acid selected from the group consisting of L and A. In some embodiments, M11 is an amino acid selected from the group consisting of L, S, and P. In some embodiments, M12is an amino acid selected from the group consisting of L and A. In some embodiments, M13is an amino acid selected from the group consisting of L, F, and A. In some embodiments, M14is an amino acid selected from the group consisting of L and A. In ACTIVE / 131743364.1 55Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT some embodiments, M15is an amino acid selected from the group consisting of L and V. In some embodiments, M16is an amino acid selected from the group consisting of L and V. In some embodiments, M17is an amino acid selected from the group consisting of L, V, and C. In some embodiments, M18is an amino acid selected from the group consisting of L and A. In some embodiments, M19is an amino acid selected from the group consisting of L, A, and S. In some embodiments, M20is an amino acid selected from the group consisting of L, A, G, and W. In some embodiments, M21is leucine (L). In some embodiments, M22is an amino acid selected from the group consisting of S, Q, G, R, and P. In some embodiments, M23 is an amino acid selected from the group consisting of P, L, E, and G. In some embodiments, M24is an amino acid selected from the group consisting of A, V, G, and S. In some embodiments, M25is an amino acid selected from the group consisting of S, A, R, Q, and L. In some embodiments, M26is an amino acid selected from the group consisting of A, G, and S.

[0119] It is to be understood that a variant of SEQ ID NO: 13 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 2 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 3 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 4 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 5 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 6 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 7 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 8 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 9 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 10 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 11 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 12 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 13 of SEQ ID NO: 13. In some ACTIVE / 131743364.1 56Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 14 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 15 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 16 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 17 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 18 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 19 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 20 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 22 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 23 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 24 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 25 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at position 26 of SEQ ID NO: 13. The variant may also comprise any number of substitutions as provided by Formula XIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, or 26 of SEQ ID NO: 13. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 13 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, or 26 of SEQ ID NO: 13.

[0120] Variants of SEQ ID NO: 14 (Formula XIV)

[0121] In some embodiments, the signal peptide comprises an amino acid sequence represented by: N1-N2-N3-N4-N5-N6-N7-N8-N9-N10-N11-N12-N13-N14-N15-N16-N17-N18-N19-N20-N21-N22-N23- N24-N25-N26-N27(Formula XIV); wherein the identity of each of N1– N27are as provided for in Table 15 below. Table 15 ACTIVE / 131743364.1 57Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0122] In some embodiments, N1is methionine (M). In some embodiments, N2is an amino acid selected from the group consisting of A and R. In some embodiments, N3is an amino acid selected from the group consisting of L, P, G, R, and S. In some embodiments, N4is an amino acid selected from the group consisting of G, A, L, S, and R. In some embodiments, N5is an ACTIVE / 131743364.1 58Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of R, A, and P. In some embodiments, N6is an amino acid selected from the group consisting of L, S, and G. In some embodiments, N7is an amino acid selected from the group consisting of L and P. In some embodiments, N8is an amino acid selected from the group consisting of L, A, G, and P. In some embodiments, N9is leucine (L). In some embodiments, N10is an amino acid selected from the group consisting of L and A. In some embodiments, N11is an amino acid selected from the group consisting of L and A. In some embodiments, N12is leucine (L). In some embodiments, N13is an amino acid selected from the group consisting of L and A. In some embodiments, N14 is an amino acid selected from the group consisting of L and A. In some embodiments, N15is an amino acid selected from the group consisting of L, V, and A. In some embodiments, N16is leucine (L). In some embodiments, N17is an amino acid selected from the group consisting of L and V. In some embodiments, N18is an amino acid selected from the group consisting of L and V. In some embodiments, N19is an amino acid selected from the group consisting of L and A. In some embodiments, N20is an amino acid selected from the group consisting of L and S. In some embodiments, N21is an amino acid selected from the group consisting of L, G, S, and T. In some embodiments, N22is an amino acid selected from the group consisting of L, P, G, and I. In some embodiments, N23is an amino acid selected from the group consisting of P and S. In some embodiments, N24 is an amino acid selected from the group consisting of G, P, V, and A. In some embodiments, N25is an amino acid selected from the group consisting of A, V, T, and G. In some embodiments, N26is an amino acid selected from the group consisting of L and R. In some embodiments, N27is an amino acid selected from the group consisting of A and G.

[0123] It is to be understood that a variant of SEQ ID NO: 14 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XIV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 2 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 3 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 4 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 5 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 6 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at ACTIVE / 131743364.1 59Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT position 7 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 8 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 10 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 11 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 13 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 14 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 15 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 17 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 18 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 19 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 20 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 21 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 22 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 23 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 24 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 25 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 26 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at position 27 of SEQ ID NO: 14. The variant may also comprise any number of substitutions as provided by Formula XIV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 10, 11, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of SEQ ID NO: 14. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 14 and a substitution at more than one position ACTIVE / 131743364.1 60Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT corresponding to position 2, 3, 4, 5, 6, 7, 8, 10, 11, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, or 27 of SEQ ID NO: 14.

[0124] Variants of SEQ ID NO: 15 (Formula XV)

[0125] In some embodiments, the signal peptide comprises an amino acid sequence represented by: O1-O2-O3-O4-O5-O6-O7-O8-O9-O10-O11-O12-O13-O14-O15-O16-O17-O18-O19-O20-O21-O22-O23- O24-O25-O26-O27-O28(Formula XV); wherein the identity of each of O1– O28are as provided for in Table 16 below. Table 16ACTIVE / 131743364.1 61Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0126] In some embodiments, O1is methionine (M). In some embodiments, O2is an amino acid selected from the group consisting of A, L, and S. In some embodiments, O3is an amino acid selected from the group consisting of P, L, R, and G. In some embodiments, O4 is an amino acid selected from the group consisting of L, R, and P. In some embodiments, O5 is an amino acid selected from the group consisting of R, P, and G. In some embodiments, O6is an amino acid selected from the group consisting of R, P, S, and L. In some embodiments, O7is an amino acid selected from the group consisting of P, R, L, G, and K. In some embodiments, O8is an amino acid selected from the group consisting of R and L. In some embodiments, O9is an amino acid selected from the group consisting of L, A, P, V, and R. In some embodiments, O10is an amino acid selected from the group consisting of L and A. In some embodiments, O11is an amino acid selected from the group consisting of L and S. In some embodiments, O12is an amino acid selected from the group consisting of L, G, and W. In some embodiments, O13 is an amino acid selected from the group consisting of L, A, and V. In some embodiments, O14 is leucine (L). In some embodiments, O15 is an amino acid selected from the group consisting of L, V, F, and A. In some embodiments, O16is leucine (L). In some embodiments, O17is an amino acid selected from the group consisting of L, I, and A. In some embodiments, O18is leucine (L). In some embodiments, O19is an amino acid selected from the group consisting of L and V. In some embodiments, O20is an amino acid selected from the group consisting of L and G. In some embodiments, O21is an amino acid selected from the group consisting of L and A. In some embodiments, O22is an amino acid selected from the group consisting of L, A, and Q. In some embodiments, O23is an amino acid selected from the group consisting of L, P, A, and G. In some embodiments, O24is an amino acid selected from the group consisting of Q, L, A, P, and G. In some embodiments, O25 is an amino acid selected from the group consisting of P, G, and A. In some embodiments, O26 is an amino acid selected from the group consisting of A, V, T, and S. In some embodiments, O27is an amino acid ACTIVE / 131743364.1 62Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT selected from the group consisting of L and S. In some embodiments, O28is an amino acid selected from the group consisting of A, G, and S.

[0127] It is to be understood that a variant of SEQ ID NO: 15 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 2 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 3 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 4 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 5 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 6 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 7 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 8 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 9 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 10 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 11 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 12 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 13 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 15 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 17 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 19 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 20 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 21 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 22 of SEQ ID NO: 15. In some embodiments, the signal peptide ACTIVE / 131743364.1 63Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 23 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 24 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 25 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 26 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 27 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at position 28 of SEQ ID NO: 15. The variant may also comprise any number of substitutions as provided by Formula XV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 of SEQ ID NO: 15. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 15 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28 of SEQ ID NO: 15.

[0128] Variants of SEQ ID NO: 16 (Formula XVI)

[0129] In some embodiments, the signal peptide comprises an amino acid sequence represented by: P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-P15-P16-P17-P18-P19-P20-P21-P22-P23-P24-P25-P26- P27-P28-P29(Formula XVI); wherein the identity of each of P1– P29are as provided for in Table 17 below. Table 17ACTIVE / 131743364.1 64Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0130] In some embodiments, P1is methionine (M). In some embodiments, P2is an amino acid selected from the group consisting of P, R, A, and E. In some embodiments, P3is an amino acid selected from the group consisting of A, R, S, P, and G. In some embodiments, P4 is an amino acid selected from the group consisting of S, A, R, and L. In some embodiments, P5is an amino acid selected from the group consisting of A, R, and G. In some embodiments, P6is an amino acid selected from the group consisting of P, L, G, A, and R. In some embodiments, P7is an amino acid selected from the group consisting of P, R, and L. In some embodiments, P8is an amino acid selected from the group consisting of L, G, and A. In some embodiments, P9is an amino acid selected from the group consisting of L and R. In some embodiments, P10is an amino acid selected from the group consisting of L, R, S, P, and G. In ACTIVE / 131743364.1 65Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT some embodiments, P11is an amino acid selected from the group consisting of L, R, G, and P. In some embodiments, P12is an amino acid selected from the group consisting of L, V, and A. In some embodiments, P13is an amino acid selected from the group consisting of L, C, and A. In some embodiments, P14is an amino acid selected from the group consisting of L and A. In some embodiments, P15is an amino acid selected from the group consisting of L and V. In some embodiments, P16is an amino acid selected from the group consisting of L and A. In some embodiments, P17is an amino acid selected from the group consisting of L, A, and V. In some embodiments, P18 is an amino acid selected from the group consisting of L and A. In some embodiments, P19is an amino acid selected from the group consisting of L and A. In some embodiments, P20is an amino acid selected from the group consisting of L, A, and V. In some embodiments, P21is an amino acid selected from the group consisting of L and A. In some embodiments, P22is an amino acid selected from the group consisting of L, S, and T. In some embodiments, P23is an amino acid selected from the group consisting of L and P. In some embodiments, P24is an amino acid selected from the group consisting of L and A. In some embodiments, P25is an amino acid selected from the group consisting of P, R, G, L, and A. In some embodiments, P26is an amino acid selected from the group consisting of G, P, S, and L. In some embodiments, P27is an amino acid selected from the group consisting of A, L, V, T, and S. In some embodiments, P28 is an amino acid selected from the group consisting of Q, A, G, R, and S. In some embodiments, P29is an amino acid selected from the group consisting of A, G, and S.

[0131] It is to be understood that a variant of SEQ ID NO: 16 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XVI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 2 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 3 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 4 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 5 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 6 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 7 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 8 of SEQ ID NO: 16. In some ACTIVE / 131743364.1 66Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 9 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 10 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 11 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 12 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 13 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 14 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 15 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 16 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 17 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 18 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 19 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 20 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 21 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 22 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 23 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 24 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 25 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 26 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 27 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 28 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at position 29 of SEQ ID NO: 16. The variant may also comprise any number of ACTIVE / 131743364.1 67Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitutions as provided by Formula XVI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at at least one position corresponding to position 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, or 29 of SEQ ID NO: 16. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 16 and a substitution at more than one position corresponding to position 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, or 29 of SEQ ID NO: 16.

[0132] Variants of SEQ ID NO: 17 (Formula XVII)

[0133] In some embodiments, the signal peptide comprises an amino acid sequence represented by: Q1-Q2-Q3-Q4-Q5-Q6-Q7-Q8-Q9-Q10-Q11-Q12-Q13-Q14-Q15-Q16-Q17-Q18-Q19-Q20-Q21-Q22-Q23- Q24-Q25-Q26-Q27-Q28-Q29-Q30(Formula XVII); wherein the identity of each of Q1– Q30are as provided for in Table 18 below. Table 18ACTIVE / 131743364.1 68Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0134] In some embodiments, Q1is methionine (M). In some embodiments, Q2is an amino acid selected from the group consisting of A, L, and S. In some embodiments, Q3is an amino acid selected from the group consisting of G and P. In some embodiments, Q4is an amino acid selected from the group consisting of P, A, and R. In some embodiments, Q5is an amino acid selected from the group consisting of R, G, A, V. In some embodiments, Q6is an amino acid selected from the group consisting of R and S. In some embodiments, Q7is an amino acid selected from the group consisting of P, R, A, and S. In some embodiments, Q8is an amino acid selected from the group consisting of A, R, G, and S. In some embodiments, Q9 is an amino acid selected from the group consisting of P and R. In some embodiments, Q10is an amino acid selected from the group consisting of A, P, and S. In some embodiments, Q11is an amino acid selected from the group consisting of G, L, and R. In some embodiments, Q12is an amino acid selected from the group consisting of L, R, V, and A. In some embodiments, Q13is an amino acid selected from the group consisting of L and T. In some embodiments, Q14is an amino acid selected from the group consisting of L, A, and R. In some embodiments, Q15is an amino acid selected from the group consisting of L and V. In some embodiments, Q16is an amino acid selected from the group consisting of L, A, and V. In some embodiments, Q17is an amino acid selected from the group consisting of L and V. In some embodiments, Q18is an amino acid selected from the group consisting of L and A. In some embodiments, Q19 is an ACTIVE / 131743364.1 69Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of L, A, and I. In some embodiments, Q20is leucine (L). In some embodiments, Q21is an amino acid selected from the group consisting of L, A, and G. In some embodiments, Q22is an amino acid selected from the group consisting of L and V. In some embodiments, Q23is an amino acid selected from the group consisting of L and V. In some embodiments, Q24is leucine (L). In some embodiments, Q25is an amino acid selected from the group consisting of A, P, S, and L. In some embodiments, Q26is an amino acid selected from the group consisting of R, L, and S. In some embodiments, Q27is an amino acid selected from the group consisting of G, P, Q, V, and L. In some embodiments, Q28is an amino acid selected from the group consisting of A, V, T, S, G, and C. In some embodiments, Q29is an amino acid selected from the group consisting of A, L, and G. In some embodiments, Q30is an amino acid selected from the group consisting of A and G.

[0135] It is to be understood that a variant of SEQ ID NO: 17 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XVII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 2 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 3 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 4 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 5 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 6 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 7 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 8 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 9 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 10 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 11 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 12 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 13 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a ACTIVE / 131743364.1 70Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution at position 14 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 15 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 16 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 17 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 18 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 19 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 21 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 22 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 23 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 25 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 26 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 27 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 28 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 29 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at position 30 of SEQ ID NO: 17. The variant may also comprise any number of substitutions as provided by Formula XVII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 25, 26, 27, 28, 29, or 30 of SEQ ID NO: 17. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 17 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 25, 26, 27, 28, 29, or 30 of SEQ ID NO: 17.

[0136] Variants of SEQ ID NO: 18 (Formula XVIII)

[0137] In some embodiments, the signal peptide comprises an amino acid sequence represented by: ACTIVE / 131743364.1 71Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT R1-R2-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-R17-R18-R19-R20-R21-R22-R23-R24- R25-R26-R27-R28-R29-R30-R31(Formula XVIII); wherein the identity of each of R1– R31are as provided for in Table 19 below. Table 19ACTIVE / 131743364.1 72Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0138] In some embodiments, R1is methionine (M). In some embodiments, R2is an amino acid selected from the group consisting of A, G, and S. In some embodiments, R3 is an amino acid selected from the group consisting of A, P, R, and L. In some embodiments, R4is an amino acid selected from the group consisting of L, P, and A. In some embodiments, R5is an amino acid selected from the group consisting of G, A, S, and R. In some embodiments, R6is an amino acid selected from the group consisting of G, A, R, and L. In some embodiments, R7is an amino acid selected from the group consisting of R, G, L, and T. In some embodiments, R8is an amino acid selected from the group consisting of R, S, and G. In some embodiments, R9is an amino acid selected from the group consisting of A, P, G, and L. In some embodiments, R10is an amino acid selected from the group consisting of A, L, G, and R. In some embodiments, R11is an amino acid selected from the group consisting of R, L, A, and C. In some embodiments, R12 is an amino acid selected from the group consisting of A, P, L, G, S, and R. In some embodiments, R13is an amino acid selected from the group consisting of L and R. In some embodiments, R14is an amino acid selected from the group consisting of L and A. In some embodiments, R15is an amino acid selected from the group consisting of L, A, and I. In some embodiments, R16is an amino acid selected from the group consisting of L and G. In some embodiments, R17is an amino acid selected from the group consisting of L, A, V, P, and S. In some embodiments, R18is an amino acid selected from the group consisting of L and A. In some embodiments, R19is an amino acid selected from the group consisting of L and A. In some embodiments, R20is an amino acid selected from the group consisting of L, A, and V. In some embodiments, R21is leucine (L). In some embodiments, R22is an amino acid selected from the group consisting of L and G. In some embodiments, R23 is an amino acid selected from the group consisting of L, A, and S. In some embodiments, R24is an amino acid selected from the group consisting of L, V, and S. In some embodiments, R25is an amino acid selected from the group consisting of L, G, and A. In some embodiments, R26is an amino acid selected from the group consisting of L, P, and V. In some embodiments, R27is an amino acid selected from the group consisting of S, A, R, G, and L. In some embodiments, R28is an ACTIVE / 131743364.1 73Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of P and G. In some embodiments, R29is an amino acid selected from the group consisting of A, S, V, and G. In some embodiments, R30is an amino acid selected from the group consisting of S, A, and R. In some embodiments, R31is an amino acid selected from the group consisting of A and G.

[0139] It is to be understood that a variant of SEQ ID NO: 18 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XVIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 2 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 3 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 4 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 5 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 6 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 7 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 8 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 9 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 10 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 11 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 12 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 13 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 14 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 15 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 16 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 17 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 18 of SEQ ID NO: 18. In some ACTIVE / 131743364.1 74Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 19 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 20 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 22 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 23 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 24 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 25 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 26 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 27 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 28 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 29 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 30 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at position 31 of SEQ ID NO: 18. The variant may also comprise any number of substitutions as provided by Formula XVIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 of SEQ ID NO: 18. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 18 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31 of SEQ ID NO: 18.

[0140] Variants of SEQ ID NO: 19 (Formula XIX)

[0141] In some embodiments, the signal peptide comprises an amino acid sequence represented by: S1-S2-S3-S4-S5-S6-S7-S8-S9-S10-S11-S12-S13-S14-S15-S16-S17-S18-S19-S20-S21-S22-S23-S24-S25-S26- S27-S28-S29-S30-S31-S32(Formula XIX); wherein the identity of each of S1– S32are as provided for in Table 20 below. ACTIVE / 131743364.1 75Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT Table 20ACTIVE / 131743364.1 76Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0142] In some embodiments, S1 is methionine (M). In some embodiments, S2 is an amino acid selected from the group consisting of A, R, G, and V. In some embodiments, S3is an amino acid selected from the group consisting of A and S. In some embodiments, S4is an amino acid selected from the group consisting of S, P, and R. In some embodiments, S5is an amino acid selected from the group consisting of P, S, and R. In some embodiments, S6is an amino acid selected from the group consisting of A, G, R, and L. In some embodiments, S7is an amino acid selected from the group consisting of L and P. In some embodiments, S8is an amino acid selected from the group consisting of R and G. In some embodiments, S9is an amino acid selected from the group consisting of G, M, and A. In some embodiments, S10is an amino acid selected from the group consisting of R and P. In some embodiments, S11is an amino acid selected from the group consisting of A, G, and R. In some embodiments, S12 is glycine (G). In some embodiments, S13is an amino acid selected from the group consisting of P, G, and S. In some embodiments, S14is an amino acid selected from the group consisting of R, G, L, and A. In some embodiments, S15is an amino acid selected from the group consisting of L, H, and S. In some embodiments, S16is an amino acid selected from the group consisting of L and G. In some embodiments, S17is an amino acid selected from the group consisting of L and F. In some embodiments, S18is an amino acid selected from the group consisting of L and A. In some embodiments, S19is an amino acid selected from the group consisting of L and A. In some embodiments, S20is an amino acid selected from the group consisting of L, A, and S. In some embodiments, S21 is an amino acid selected from the group consisting of L and V. In some embodiments, S22 is leucine (L). In some embodiments, S23 is an amino acid selected from the group consisting of L, A, and G. In some embodiments, S24is an amino acid selected from the group consisting of L, A, and G. In some embodiments, S25is an amino acid selected from the group consisting of L and A. In some embodiments, S26is an amino acid selected from the group consisting of L, A, and F. In some embodiments, S27is an amino acid selected from the group consisting of L and V. In some embodiments, S28is an amino acid selected from the group consisting of P, R, and A. In some embodiments, S29is an amino acid selected from the group consisting of G and V. In some embodiments, S30is an amino acid selected ACTIVE / 131743364.1 77Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT from the group consisting of V, A, T, and S. In some embodiments, S31is an amino acid selected from the group consisting of L, G, and R. In some embodiments, S32is alanine (A).

[0143] It is to be understood that a variant of SEQ ID NO: 19 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XIX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 2 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 3 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 4 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 5 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 6 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 7 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 8 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 9 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 10 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 11 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 13 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 14 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 15 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 16 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 17 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 18 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 19 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 20 of SEQ ID NO: 19. In some embodiments, the signal peptide ACTIVE / 131743364.1 78Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 21 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 23 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 24 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 25 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 26 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 27 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 28 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 29 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 30 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at position 31 of SEQ ID NO: 19. The variant may also comprise any number of substitutions as provided by Formula XIX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 28, 29, 30, or 31 of SEQ ID NO: 19. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 19 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 28, 29, 30, or 31 of SEQ ID NO: 19.

[0144] Variants of SEQ ID NO: 20 (Formula XX)

[0145] In some embodiments, the signal peptide comprises an amino acid sequence represented by: T1-T2-T3-T4-T5-T6-T7-T8-T9-T10-T11-T12-T13-T14-T15-T16-T17-T18-T19-T20-T21-T22-T23-T24-T25- T26-T27-T28-T29-T30-T31-T32-T33 (Formula XX); wherein the identity of each of T1– T33are as provided for in Table 21 below. Table 21ACTIVE / 131743364.1 79Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENTACTIVE / 131743364.1 80Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0146] In some embodiments, T1is methionine (M). In some embodiments, T2is an amino acid selected from the group consisting of A, R, and L. In some embodiments, T3is an amino acid selected from the group consisting of A, G, and K. In some embodiments, T4is an amino acid selected from the group consisting of L, A, T, and R. In some embodiments, T5is an amino acid selected from the group consisting of P and G. In some embodiments, T6is an amino acid selected from the group consisting of R, P, and G. In some embodiments, T7is an amino acid selected from the group consisting of L, S, R, and G. In some embodiments, T8is an amino acid selected from the group consisting of G, P, and R. In some embodiments, T9is an amino acid selected from the group consisting of S, and G. In some embodiments, T10is serine (S). In some embodiments, T11 is an amino acid selected from the group consisting of A and M. In some embodiments, T12is an amino acid selected from the group consisting of L, A, and P. In some embodiments, T13is an amino acid selected from the group consisting of P and A. In some embodiments, T14is an amino acid selected from the group consisting of L, S, G, and V. In some embodiments, T15is an amino acid selected from the group consisting of R, S, and A. In some embodiments, T16is an amino acid selected from the group consisting of L, P, A, and V. In some embodiments, T17is an amino acid selected from the group consisting of L and A. In some embodiments, T18is an amino acid selected from the group consisting of L and W. In some embodiments, T19is an amino acid selected from the group consisting of A, S, and L. In some embodiments, T20is an amino acid selected from the group consisting of L and T. In some embodiments, T21 is an amino acid selected from the group consisting of L, I, and A. In some embodiments, T22is an amino acid selected from the group consisting of L and A. In some embodiments, T23is an amino acid selected from the group consisting of L and V. In some embodiments, T24is an amino acid selected from the group consisting of L, A, and S. In some embodiments, T25is an amino acid selected from the group consisting of L and A. In some embodiments, T26is an amino acid selected from the group consisting of L and A. In some embodiments, T27is an amino acid selected from the group consisting of L, W, and F. In some embodiments, T28is an amino acid selected from the group consisting of P and V. In some embodiments, T29is an amino acid selected from the group consisting of P and G. In some embodiments, T30is an amino acid selected from the group consisting of P, L, and Q. In some embodiments, T31 is an amino acid selected from the group consisting of A, G, and V. ACTIVE / 131743364.1 81Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT In some embodiments, T32is an amino acid selected from the group consisting of L and A. In some embodiments, T33is an amino acid selected from the group consisting of A and G.

[0147] It is to be understood that a variant of SEQ ID NO: 20 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 2 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 3 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 4 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 5 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 6 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 7 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 8 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 9 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 11 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 12 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 13 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 14 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 15 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 16 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 17 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 18 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 19 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 20 of SEQ ID NO: 20. In some embodiments, the signal peptide ACTIVE / 131743364.1 82Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 21 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 22 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 23 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 24 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 25 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 26 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 27 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 28 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 29 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 30 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 31 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 32 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at position 33 of SEQ ID NO: 20. The variant may also comprise any number of substitutions as provided by Formula XX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 of SEQ ID NO: 20. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 20 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 of SEQ ID NO: 20.

[0148] Variants of SEQ ID NO: 21 (Formula XXI)

[0149] In some embodiments, the signal peptide comprises an amino acid sequence represented by: U1-U2-U3-U4-U5-U6-U7-U8-U9-U10-U11-U12-U13-U14-U15-U16-U17-U18-U19-U20-U21-U22-U23- U24-U25-U26-U27-U28-U29-U30-U31-U32-U33-U34(Formula XXI); ACTIVE / 131743364.1 83Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT wherein the identity of each of U1– U34are as provided for in Table 22 below. Table 22ACTIVE / 131743364.1 84Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0150] In some embodiments, U1is methionine (M). In some embodiments, U2is an amino acid selected from the group consisting of G, A, and S. In some embodiments, U3is an amino acid selected from the group consisting of P, L, and R. In some embodiments, U4 is an amino acid selected from the group consisting of L, P, and A. In some embodiments, U5is an amino acid selected from the group consisting of S, P, and E. In some embodiments, U6is an amino acid selected from the group consisting of A, R, and L. In some embodiments, U7is an amino acid selected from the group consisting of P and S. In some embodiments, U8is an amino acid selected from the group consisting of P, R, and A. In some embodiments, U9is an amino acid selected from the group consisting of C, G, A, P. In some embodiments, U10is an amino acid selected from the group consisting of T and P. In some embodiments, U11is an amino acid selected from the group consisting of Q, S, and R. In some embodiments, U12is an amino acid selected from the group consisting of R, H, N, and S. In some embodiments, U13 is an amino acid selected from the group consisting of I and P. In some embodiments, U14 is an amino acid selected from the group consisting of T, R, G, and K. In some embodiments, U15is an amino acid selected from the group consisting of W, L, P, Q. In some embodiments, U16is an amino acid selected from the group consisting of K, L, V, and P. In some embodiments, U17is an amino acid selected from the group consisting of G, P, R, A, and L. In some embodiments, U18is an amino acid selected from the group consisting of L, V, A, and H. In some embodiments, U19is an amino acid selected from the group consisting of L and A. In some embodiments, U20is leucine (L). In some embodiments, U21is an amino acid selected from the group consisting of L and T. In some embodiments, U22is an amino acid selected from the group consisting of L and A. In some embodiments, U23 is an amino acid selected from the group consisting of L and S. In some embodiments, U24 is leucine (L). In some embodiments, U25is leucine (L). In some embodiments, U26is an amino acid selected from the group consisting of N, L, V, and A. In some embodiments, U27is an amino acid selected from the group consisting of F, L, and A. In some embodiments, U28is an amino acid selected from the ACTIVE / 131743364.1 85Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT group consisting of W, A, and L. In some embodiments, U29is an amino acid selected from the group consisting of N, L, and S. In some embodiments, U30is an amino acid selected from the group consisting of L, P, A, and R. In some embodiments, U31is an amino acid selected from the group consisting of P and R. In some embodiments, U32is an amino acid selected from the group consisting of T and A. In some embodiments, U33is an amino acid selected from the group consisting of T, L, A, and Q. In some embodiments, U34is an amino acid selected from the group consisting of A and G.

[0151] It is to be understood that a variant of SEQ ID NO: 21 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 2 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 3 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 4 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 5 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 6 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 7 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 8 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 9 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 10 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 11 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 12 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 13 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 14 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 15 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 16 of SEQ ID NO: 21. In some embodiments, ACTIVE / 131743364.1 86Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 17 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 18 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 19 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 21 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 22 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 23 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 26 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 27 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 28 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 29 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 30 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 31 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 32 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 33 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at position 34 of SEQ ID NO: 21. The variant may also comprise any number of substitutions as provided by Formula XXI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 26, 27, 28, 29, 30, 31, 32, 33, or 34 of SEQ ID NO: 21. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 21 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 21, 22, 23, 26, 27, 28, 29, 30, 31, 32, 33, or 34 of SEQ ID NO: 21.

[0152] Variants of SEQ ID NO: 22 (Formula XXII) ACTIVE / 131743364.1 87Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0153] In some embodiments, the signal peptide comprises an amino acid sequence represented by: V1-V2-V3-V4-V5-V6-V7-V8-V9-V10-V11-V12-V13-V14-V15-V16-V17-V18-V19-V20-V21-V22-V23- V24-V25-V26-V27-V28-V29-V30-V31-V32-V33-V34-V35(Formula XXII); wherein the identity of each of V1– V35are as provided for in Table 23 below. Table 23ACTIVE / 131743364.1 88Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0154] In some embodiments, V1is methionine (M). In some embodiments, V2is an amino acid selected from the group consisting of A, R, and R. In some embodiments, V3is an amino acid selected from the group consisting of P and S. In some embodiments, V4is an amino acid selected from the group consisting of R, A, W, and P. In some embodiments, V5is an amino acid selected from the group consisting of A, R, and T. In some embodiments, V6is an amino acid selected from the group consisting of R and G. In some embodiments, V7 is an amino acid selected from the group consisting of R and Q. In some embodiments, V8is an amino acid selected from the group consisting of R, G, P, and V. In some embodiments, V9is an amino acid selected from the group consisting of S, G, and K. In some embodiments, V10is an amino acid selected from the group consisting of P, R, A, and L. In some embodiments, V11is an amino acid selected from the group consisting of R and G. In some embodiments, V12is an amino acid selected from the group consisting of R and L. In some embodiments, V13is an amino acid selected from the group consisting of V, R, G, A, and P. In some embodiments, V14is an amino acid selected from the group consisting of P and L. In some embodiments, V15is an amino acid selected from the group consisting of G, L, A, and P. In some embodiments, V16 is an amino acid selected from the group consisting of L and P. In some embodiments, V17 is an amino acid selected from the group consisting of G, P, and L. In some embodiments, V18is an amino acid selected from the group consisting of P and W. In some embodiments, V19is an amino acid selected from the group consisting of G and R. In some embodiments, V20is an amino acid selected from the group consisting of A, P, and L. In some embodiments, V21is an amino acid selected from the group consisting of L and P. In some embodiments, V22is an ACTIVE / 131743364.1 89Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of L and A. In some embodiments, V23is an amino acid selected from the group consisting of L and S. In some embodiments, V24is an amino acid selected from the group consisting of L and V. In some embodiments, V25is leucine (L). In some embodiments, V26is leucine (L). In some embodiments, V27is an amino acid selected from the group consisting of F, L, and V. In some embodiments, V28is leucine (L). In some embodiments, V29is an amino acid selected from the group consisting of L and G. In some embodiments, V30is an amino acid selected from the group consisting of L, P, and V. In some embodiments, V31 is an amino acid selected from the group consisting of G, A, and L. In some embodiments, V32is an amino acid selected from the group consisting of G and A. In some embodiments, V33is an amino acid selected from the group consisting of G, A, and V. In some embodiments, V34is an amino acid selected from the group consisting of A, V, R, and Q. In some embodiments, V35is an amino acid selected from the group consisting of A and G.

[0155] It is to be understood that a variant of SEQ ID NO: 22 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 2 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 3 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 4 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 5 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 6 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 7 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 8 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 9 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 10 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 11 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 12 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 13 of SEQ ID NO: 22. In some ACTIVE / 131743364.1 90Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 14 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 15 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 16 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 17 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 18 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 19 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 20 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 21 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 22 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 23 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 24 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 27 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 29 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 30 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 31 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 32 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 33 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 34 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at position 35 of SEQ ID NO: 22. The variant may also comprise any number of substitutions as provided by Formula XXII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, ACTIVE / 131743364.1 91Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT 23, 24, 27, 29, 30, 31, 32, 33, 34, or 35 of SEQ ID NO: 22. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 22 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 27, 29, 30, 31, 32, 33, 34, or 35 of SEQ ID NO: 22.

[0156] Variants of SEQ ID NO: 23 (Formula XXIII)

[0157] In some embodiments, the signal peptide comprises an amino acid sequence represented by: W1-W2-W3-W4-W5-W6-W7-W8-W9-W10-W11-W12-W13-W14-W15-W16-W17-W18-W19-W20- W21-W22-W23-W24-W25-W26-W27-W28-W29-W30-W31-W32-W33-W34-W35-W36(Formula XXIII); wherein the identity of each of W1– W36are as provided for in Table 24 below. Table 24ACTIVE / 131743364.1 92Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0158] In some embodiments, W1 is methionine (M). In some embodiments, W2 is an amino acid selected from the group consisting of S, A, and N. In some embodiments, W3is an amino acid selected from the group consisting of A and L. In some embodiments, W4is an amino acid selected from the group consisting of A, N, L, and P. In some embodiments, W5is an amino acid selected from the group consisting of S, A, and K. In some embodiments, W6is an amino acid selected from the group consisting of S, R, and D. In some embodiments, W7is an amino acid selected from the group consisting of R, P, and E. In some embodiments, W8is an amino acid selected from the group consisting of R and A. In some embodiments, W9is an amino acid selected from the group consisting of A, G, and L. In some embodiments, W10is an amino acid selected from the group consisting of R and K. In some embodiments, W11 is an amino acid selected from the group consisting of A and V. In some embodiments, W12 is an amino acid selected from the group consisting of P, L, and R. In some embodiments, W13is an amino acid selected from the group consisting of G and S. In some embodiments, W14is an amino acid selected from the group consisting of P and Q. In some embodiments, W15is an ACTIVE / 131743364.1 93Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of S, V, and D. In some embodiments, W16is an amino acid selected from the group consisting of L, F, S, and G. In some embodiments, W17is an amino acid selected from the group consisting of S, P, and H. In some embodiments, W18is an amino acid selected from the group consisting of L and P. In some embodiments, W19is an amino acid selected from the group consisting of C, T, and F. In some embodiments, W20is an amino acid selected from the group consisting of P and A. In some embodiments, W21is an amino acid selected from the group consisting of L and A. In some embodiments, W22 is leucine (L). In some embodiments, W23 is an amino acid selected from the group consisting of L, M, V, and A. In some embodiments, W24is an amino acid selected from the group consisting of L and M. In some embodiments, W25is leucine (L). In some embodiments, W26is an amino acid selected from the group consisting of L and S. In some embodiments, W27is an amino acid selected from the group consisting of L, R, and M. In some embodiments, W28is an amino acid selected from the group consisting of L, V, and T. In some embodiments, W29is an amino acid selected from the group consisting of T, L, and M. In some embodiments, W30is an amino acid selected from the group consisting of P, L, and Q. In some embodiments, W31is an amino acid selected from the group consisting of P, A, and F. In some embodiments, W32is an amino acid selected from the group consisting of G, C, and L. In some embodiments, W33 is an amino acid selected from the group consisting of P and G. In some embodiments, W34is an amino acid selected from the group consisting of A, V, I, and L. In some embodiments, W35is an amino acid selected from the group consisting of T and A. In some embodiments, W36is an amino acid selected from the group consisting of S, A, and G.

[0159] It is to be understood that a variant of SEQ ID NO: 23 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 2 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 3 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 4 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 5 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 6 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 7 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino ACTIVE / 131743364.1 94Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT acid sequence of SEQ ID NO: 23 and a substitution at position 8 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 9 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 10 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 11 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 12 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 13 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 14 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 15 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 16 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 17 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 18 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 19 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 20 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 21 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 23 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 24 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 25 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 26 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 27 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 28 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 29 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a ACTIVE / 131743364.1 95Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution at position 30 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 31 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 32 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 33 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 34 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 35 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at position 36 of SEQ ID NO: 23. The variant may also comprise any number of substitutions as provided by Formula XXIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 of SEQ ID NO: 23. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 23 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, or 36 of SEQ ID NO: 23.

[0160] Variants of SEQ ID NO: 24 (Formula XXIV)

[0161] In some embodiments, the signal peptide comprises an amino acid sequence represented by: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-X23- X24-X25-X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37(Formula XXIV); wherein the identity of each of X1– X37are as provided for in Table 25 below. Table 25ACTIVE / 131743364.1 96Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENTACTIVE / 131743364.1 97Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0162] In some embodiments, X1is methionine (M). In some embodiments, X2is an amino acid selected from the group consisting of A, D, P, S, and W. In some embodiments, X3is an amino acid selected from the group consisting of L, V, A, and K. In some embodiments, X4is an amino acid selected from the group consisting of G, H, P, and W. In some embodiments, X5is an amino acid selected from the group consisting of Q, T, R, S, and I. In some embodiments, X6is an amino acid selected from the group consisting of R, K, S, and L. In some embodiments, X7is an amino acid selected from the group consisting of L, W, G, R, and T. In some embodiments, X8 is an amino acid selected from the group consisting of F, K, P, A, and H. In some embodiments, X9is an amino acid selected from the group consisting of A, I, and C. In some embodiments, X10is an amino acid selected from the group consisting of R, A, and T. In some embodiments, X11is an amino acid selected from the group consisting of S, M, Q, and V. In some embodiments, X12is an amino acid selected from the group consisting of S, A, and P. In some embodiments, X13is an amino acid selected from the group consisting of R, L, A, G, and F. In some embodiments, X14is an amino acid selected from the group consisting of R, P, and G. In some embodiments, X15is an amino acid selected from the group consisting of A, P, R, S, and H. In some embodiments, X16is an amino acid selected from the group consisting of G, P, and L. In some embodiments, X17is an amino acid selected from the group consisting of P, R, A, and S. In some embodiments, X18 is an amino acid selected from the group consisting of L, P, and G. In some embodiments, X19is an amino acid selected from the group consisting of L, C, and Q. In some embodiments, X20is an amino acid selected from the group consisting of L, G, A, and C. In some embodiments, X21is an amino acid selected from the group consisting of P, T, L, and C. In some embodiments, X22is an amino acid selected from the group consisting of L, P, and C. In some embodiments, X23is an amino acid selected from the group consisting of L, W, A, and C. In some embodiments, X24is an amino acid selected from the group consisting of L, A, and F. In some embodiments, X25is leucine (L). In some embodiments, X26is an amino acid selected from the group consisting of L and V. In some embodiments, X27is an amino acid selected from the group consisting of L, F, and C. In some embodiments, X28 is an amino acid selected from the group consisting of L, V, and F. In some embodiments, X29is an amino acid selected from the group consisting of L, G, W, and T. In some embodiments, X30is an amino acid selected from the group consisting of I, A, G, P, and V. In some embodiments, X31is an amino acid selected from the group consisting of P, L, A, and S. In some embodiments, X32is an amino acid selected from the group consisting of P, V, G, and S. In some embodiments, X33is an amino acid selected from the group consisting ofP, G, R, and V. In some embodiments, X34is an amino acid selected from ACTIVE / 131743364.1 98Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT the group consisting of M, S, A, L, and P. In some embodiments, X35is an amino acid selected from the group consisting of V, R, G, and A. In some embodiments, X36is an amino acid selected from the group consisting of S, V, A, and T. In some embodiments, X37is an amino acid selected from the group consisting of A, P, G, and C.

[0163] It is to be understood that a variant of SEQ ID NO: 24 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXIV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 2 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 3 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 4 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 5 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 6 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 7 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 8 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 9 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 10 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 11 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 12 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 13 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 14 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 15 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 16 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 17 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 18 of SEQ ID NO: 24. In some ACTIVE / 131743364.1 99Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 19 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 20 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 21 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 22 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 23 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 24 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 26 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 27 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 28 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 29 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 30 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 31 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 32 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 33 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 34 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 35 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 36 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at position 37 of SEQ ID NO: 24. The variant may also comprise any number of substitutions as provided by Formula XXIV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 24 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, or 37 of SEQ ID NO: 24. In some embodiments, the signal peptide comprises the amino acid sequence ACTIVE / 131743364.1 100Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT of SEQ ID NO: 24 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, or 37 of SEQ ID NO: 24.

[0164] Variants of SEQ ID NO: 25 (Formula XXV)

[0165] In some embodiments, the signal peptide comprises an amino acid sequence represented by: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15-Y16-Y17-Y18-Y19-Y20-Y21-Y22-Y23- Y24-Y25-Y26-Y27-Y28-Y29-Y30-Y31-Y32-Y33-Y34-Y35-Y36-Y37-Y38 (Formula XXV); wherein the identity of each of Y1– Y38are as provided for in Table 26 below. Table 26ACTIVE / 131743364.1 101Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0166] In some embodiments, Y1 is methionine (M). In some embodiments, Y2 is an amino acid selected from the group consisting of G, W, A, I, and L. In some embodiments, Y3is an amino acid selected from the group consisting of S, R, T, and I. In some embodiments, Y4is an amino acid selected from the group consisting of E, K, W, D, T, L, and V. In some embodiments, Y5is an amino acid selected from the group consisting of R, S, G, E, and H. In some embodiments, Y6is an amino acid selected from the group consisting of S, L, A, I, and T. In some embodiments, Y7is an amino acid selected from the group consisting of P, S, R, C, V, and E. In some embodiments, Y8is an amino acid selected from the group consisting of R, N, H, I, L, and G. In some embodiments, Y9is an amino acid selected from the group consisting of R, P, V, M, and G. In some embodiments, Y10 is an amino acid selected from the group consisting of R, P, G, T, S, and H. In some embodiments, Y11 is an amino acid selected from the group consisting of F, A, E, L, S, and C In some embodiments, Y12is an amino acid selected from the group consisting of P, C, K, T, and S. In some embodiments, Y13is an amino acid selected from the group consisting of L, C, Q, A, and F. In some embodiments, Y14is an ACTIVE / 131743364.1 102Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of L, R, Q, G, and H. In some embodiments, Y15is an amino acid selected from the group consisting of S, V, N, H, Q, and L. In some embodiments, Y16is an amino acid selected from the group consisting of A, R, S, V, T, and P. In some embodiments, Y17is an amino acid selected from the group consisting of T, S, H, G, A, and K. In some embodiments, Y18is an amino acid selected from the group consisting of A, G, K, M, S, and F. In some embodiments, Y19is an amino acid selected from the group consisting of A, M, T, L, and S. In some embodiments, Y20is an amino acid selected from the group consisting of A, P, Q, R, S, and W. In some embodiments, Y21 is an amino acid selected from the group consisting of P, E, L, A, T, and R. In some embodiments, Y22is an amino acid selected from the group consisting of G, S, R, P, L, and N. In some embodiments, Y23is an amino acid selected from the group consisting of V, P, and L. In some embodiments, Y24is an amino acid selected from the group consisting of L, S, G, W, and A. In some embodiments, Y25is an amino acid selected from the group consisting of L, A, S, and F. In some embodiments, Y26is an amino acid selected from the group consisting of L, Q, and V. In some embodiments, Y27is an amino acid selected from the group consisting of L, S, V, C, and I. In some embodiments, Y28is an amino acid selected from the group consisting of L, F, A, and V. In some embodiments, Y29is an amino acid selected from the group consisting of L, A, and I. In some embodiments, Y30 is an amino acid selected from the group consisting of L, H, A, and S. In some embodiments, Y31is an amino acid selected from the group consisting of C, S, A, V, W, F, and L. In some embodiments, Y32is an amino acid selected from the group consisting of L, F, G, C, S, and A. In some embodiments, Y33is an amino acid selected from the group consisting of L, A, T, and V. In some embodiments, Y34is an amino acid selected from the group consisting of G, M, T, A, Q, and E. In some embodiments, Y35is an amino acid selected from the group consisting of A, S, H, Y, and W. In some embodiments, Y36is an amino acid selected from the group consisting of T, V, S, A, and C. In some embodiments, Y37is an amino acid selected from the group consisting of R, T, A, N, Y, and S. In some embodiments, Y38is an amino acid selected from the group consisting of A and G.

[0167] It is to be understood that a variant of SEQ ID NO: 25 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 2 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 3 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a ACTIVE / 131743364.1 103Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution at position 4 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 5 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 6 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 7 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 8 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 9 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 10 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 11 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 12 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 13 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 14 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 15 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 16 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 17 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 18 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 19 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 20 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 21 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 22 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 23 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 24 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 25 of SEQ ACTIVE / 131743364.1 104Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 26 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 27 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 28 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 29 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 30 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 31 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 32 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 33 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 34 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 35 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 36 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 37 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at position 38 of SEQ ID NO: 25. The variant may also comprise any number of substitutions as provided by Formula XXV. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at at least one position corresponding to position 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, or 38 of SEQ ID NO: 25. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 25 and a substitution at more than one position corresponding to position 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, or 38 of SEQ ID NO: 25.

[0168] Variants of SEQ ID NO: 26 (Formula XXVI)

[0169] In some embodiments, the signal peptide comprises an amino acid sequence represented by: Z1-Z2-Z3-Z4-Z5-Z6-Z7-Z8-Z9-Z10-Z11-Z12-Z13-Z14-Z15-Z16-Z17-Z18-Z19-Z20-Z21-Z22-Z23-Z24-Z25- Z26-Z27-Z28-Z29-Z30-Z31-Z32-Z33-Z34-Z35-Z36-Z37-Z38-Z39(Formula XXVI); ACTIVE / 131743364.1 105Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT wherein the identity of each of Z1– Z39are as provided for in Table 27 below. Table 27ACTIVE / 131743364.1 106Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0170] In some embodiments, Z1is methionine (M). In some embodiments, Z2is an amino acid selected from the group consisting of L, A, and E. In some embodiments, Z3is an amino acid selected from the group consisting of C, L, V, and W. In some embodiments, Z4is an amino acid selected from the group consisting of I, G, L, and F. In some embodiments, Z5is an amino acid selected from the group consisting of Y, L, R, and S. In some embodiments, Z6is an amino acid selected from the group consisting of G, P, and C. In some embodiments, Z7 is an amino acid selected from the group consisting of T, G, R, and V. In some embodiments, Z8is an amino acid selected from the group consisting of L, T, and G. In some embodiments, Z9is an amino acid selected from the group consisting of F, S, G, and A. In some embodiments, Z10is an amino acid selected from the group consisting of T, Y, and L. In some embodiments, Z11is an amino acid selected from the group consisting of T, L, S, and A. In some embodiments, Z12is an amino acid selected from the group consisting of S, F, and E. In some embodiments, Z13is an amino acid selected from the group consisting of L, H, P, and R. In some embodiments, Z14is an amino acid selected from the group consisting of P, C, K, and Y. In some embodiments, Z15is an amino acid selected from the group consisting of T, P, L, and C. In some embodiments, Z16 is an amino acid selected from the group consisting of K, W, D, and R. In some embodiments, Z17 is an amino acid selected from the group consisting of S, P, N, and R. In some embodiments, Z18is an amino acid selected from the group consisting of L, R, and S. In some embodiments, Z19is an amino acid selected from the group consisting of N, Q, V, and P. In some embodiments, Z20is an amino acid selected from the group consisting of ACTIVE / 131743364.1 107Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT M, Q, P, and G. In some embodiments, Z21is an amino acid selected from the group consisting of G, P, K, and I. In some embodiments, Z22is an amino acid selected from the group consisting of I, A, G, and T. In some embodiments, Z23is an amino acid selected from the group consisting of S, L, K, and C. In some embodiments, Z24is an amino acid selected from the group consisting of L, W, M, and C. In some embodiments, Z25is an amino acid selected from the group consisting of T, P, K, and V. In some embodiments, Z26is an amino acid selected from the group consisting of T, I, and L. In some embodiments, Z27is an amino acid selected from the group consisting of L and I. In some embodiments, Z28 is an amino acid selected from the group consisting of L and A. In some embodiments, Z29is an amino acid selected from the group consisting of I, A, V, and L. In some embodiments, Z30is an amino acid selected from the group consisting of L, F, and N. In some embodiments, Z31is an amino acid selected from the group consisting of S, A, L, and C. In some embodiments, Z32is an amino acid selected from the group consisting of V, L, G, and S. In some embodiments, Z33is an amino acid selected from the group consisting of L, A, and G. In some embodiments, Z34is an amino acid selected from the group consisting of V, S, and L. In some embodiments, Z35is an amino acid selected from the group consisting of L, S, G, and P. In some embodiments, Z36is an amino acid selected from the group consisting of L, V, N, and M. In some embodiments, Z37is an amino acid selected from the group consisting of S and A. In some embodiments, Z38 is an amino acid selected from the group consisting of T, E, V, and L. In some embodiments, Z39is alanine (A).

[0171] It is to be understood that a variant of SEQ ID NO: 26 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXVI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 2 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 3 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 4 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 5 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 6 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 7 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 8 of SEQ ID NO: 26. In some ACTIVE / 131743364.1 108Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 9 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 10 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 11 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 12 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 13 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 14 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 15 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 16 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 17 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 18 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 19 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 20 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 21 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 22 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 23 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 24 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 25 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 26 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 27 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 28 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 29 of SEQ ID NO: 26. In some embodiments, the signal peptide ACTIVE / 131743364.1 109Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 30 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 31 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 32 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 33 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 34 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 35 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 36 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 37 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at position 38 of SEQ ID NO: 26. The variant may also comprise any number of substitutions as provided by Formula XXVI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at at least one position corresponding to position 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, or 38 of SEQ ID NO: 26. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 26 and a substitution at more than one position corresponding to position 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, or 38 of SEQ ID NO: 26.

[0172] Variants of SEQ ID NO: 27 (Formula XXVII)

[0173] In some embodiments, the signal peptide comprises an amino acid sequence represented by: (AA)1-(AA)2-(AA)3-(AA)4-(AA)5-(AA)6-(AA)7-(AA)8-(AA)9-(AA)10-(AA)11-(AA)12-(AA)13- (AA)14-(AA)15-(AA)16-(AA)17-(AA)18-(AA)19-(AA)20-(AA)21-(AA)22-(AA)23-(AA)24-(AA)25- (AA)26-(AA)27-(AA)28-(AA)29-(AA)30-(AA)31-(AA)32-(AA)33-(AA)34-(AA)35-(AA)36-(AA)37- (AA)38-(AA)39-(AA)40-(AA)41(Formula XXVII); wherein the identity of each of (AA)1– (AA)41are as provided for in Table 28 below. Table 28 ACTIVE / 131743364.1 110Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENTACTIVE / 131743364.1 111Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0174] In some embodiments, (AA)1is methionine (M). In some embodiments, (AA)2is an amino acid selected from the group consisting of R, A, G, and L. In some embodiments, (AA)3is an amino acid selected from the group consisting of H, A, R, F, and V. In some embodiments, (AA)4is an amino acid selected from the group consisting of A, G, T, M, and L. In some embodiments, (AA)5is an amino acid selected from the group consisting of S, H, A, and C. In some embodiments, (AA)6 is an amino acid selected from the group consisting of A, I, T, and G. In some embodiments, (AA)7is an amino acid selected from the group consisting of P, Q, R, and F. In some embodiments, (AA)8is an amino acid selected from the group consisting of G, N, A, and P. In some embodiments, (AA)9is an amino acid selected from the group consisting of G, A, L, and E. In some embodiments, (AA)10is an amino acid selected from the group consisting of R, C, S, and A. In some embodiments, (AA)11is an amino acid selected from the group consisting of G, R, Q, and M. In some embodiments, (AA)12is an amino acid selected from the group consisting of A, T, G, S, and P. In some embodiments, (AA)13is an amino acid selected from the group consisting of L, K, A, and S. In some embodiments, (AA)14is an amino acid selected from the group consisting of S, A, H, and G. In some embodiments, (AA)15 is an amino acid selected from the group consisting of R, A, C, P, and N. In some embodiments, (AA)16is an amino acid selected from the group consisting of F, A, R, L, and S. In some embodiments, (AA)17is an amino acid selected from the group consisting of A, V, C, and R. In some embodiments, (AA)18is an amino acid selected from the group consisting of P, V, A, and F. In some embodiments, (AA)19is an amino acid selected from the group consisting of C, R, W, H, and P. In some embodiments, (AA)20is an amino ACTIVE / 131743364.1 112Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT acid selected from the group consisting of I, G, L, S, and A. In some embodiments, (AA)21is an amino acid selected from the group consisting of S, M, G, and C. In some embodiments, (AA)22is an amino acid selected from the group consisting of S, G, P, and L. In some embodiments, (AA)23is an amino acid selected from the group consisting of G, F, Q, and A. In some embodiments, (AA)24is an amino acid selected from the group consisting of A, L, I, and P. In some embodiments, (AA)25is an amino acid selected from the group consisting of L, R, F, and G. In some embodiments, (AA)26is an amino acid selected from the group consisting of S, C, Y, and A. In some embodiments, (AA)27 is an amino acid selected from the group consisting of L, K, W, and T. In some embodiments, (AA)28is an amino acid selected from the group consisting of L, I, C, V, and Y. In some embodiments, (AA)29is an amino acid selected from the group consisting of L and A. In some embodiments, (AA)30is an amino acid selected from the group consisting of L, V, I, and A. In some embodiments, (AA)31is an amino acid selected from the group consisting of F, S, I, and L. In some embodiments, (AA)32is an amino acid selected from the group consisting of L, F, and V. In some embodiments, (AA)33is an amino acid selected from the group consisting of L, C, and A. In some embodiments, (AA)34is an amino acid selected from the group consisting of G, C, V, and H. In some embodiments, (AA)35is an amino acid selected from the group consisting of C, H, Q, M, and L. In some embodiments, (AA)36 is an amino acid selected from the group consisting of Y, L, V, M, and S. In some embodiments, (AA)37is an amino acid selected from the group consisting of V, A, G, S, and L. In some embodiments, (AA)38is an amino acid selected from the group consisting of S, L, and V. In some embodiments, (AA)39is an amino acid selected from the group consisting of A, T, L, V, and S. In some embodiments, (AA)40is an amino acid selected from the group consisting of Q, L, and F. In some embodiments, (AA)41is an amino acid selected from the group consisting of G and A.

[0175] It is to be understood that a variant of SEQ ID NO: 27 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXVII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 2 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 3 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 4 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 5 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of ACTIVE / 131743364.1 113Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT SEQ ID NO: 27 and a substitution at position 6 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 7 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 8 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 9 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 10 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 11 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 12 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 13 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 14 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 15 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 16 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 17 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 18 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 19 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 20 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 21 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 22 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 23 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 24 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 25 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 26 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at ACTIVE / 131743364.1 114Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT position 27 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 28 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 29 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 30 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 31 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 32 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 33 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 34 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 35 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 36 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 37 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 38 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 39 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 40 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at position 41 of SEQ ID NO: 27. The variant may also comprise any number of substitutions as provided by Formula XXVII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at at least one position corresponding to position 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, or 41 of SEQ ID NO: 27. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 27 and a substitution at more than one position corresponding to position 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, or 41 of SEQ ID NO: 27.

[0176] Variants of SEQ ID NO: 28 (Formula XXVIII)

[0177] In some embodiments, the signal peptide comprises an amino acid sequence represented by: ACTIVE / 131743364.1 115Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT (BB)1-(BB)2-(BB)3-(BB)4-(BB)5-(BB)6-(BB)7-(BB)8-(BB)9-(BB)10-(BB)11-(BB)12-(BB)13- (BB)14-(BB)15-(BB)16-(BB)17-(BB)18-(BB)19-(BB)20-(BB)21-(BB)22-(BB)23-(BB)24-(BB)25- (BB)26-(BB)27-(BB)28-(BB)29-(BB)30-(BB)31-(BB)32-(BB)33-(BB)34-(BB)35-(BB)36-(BB)37- (BB)38-(BB)39-(BB)40-(BB)41-(BB)42-(BB)43(Formula XXVIII); wherein the identity of each of (BB)1– (BB)43are as provided for in Table 29 below. Table 29ACTIVE / 131743364.1 116Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0178] In some embodiments, (BB)1 is methionine (M). In some embodiments, (BB)2 is an amino acid selected from the group consisting of A and P. In some embodiments, (BB)3 is an amino acid selected from the group consisting of P and G. In some embodiments, (BB)4is an amino acid selected from the group consisting of S and P. In some embodiments, (BB)5is an amino acid selected from the group consisting of P and R. In some embodiments, (BB)6is an amino acid selected from the group consisting of R and G. In some embodiments, (BB)7is an amino acid selected from the group consisting of T and A. In some embodiments, (BB)8is an amino acid selected from the group consisting of G and A. In some embodiments, (BB)9is an amino acid selected from the group consisting of S and G. In some embodiments, (BB)10is an amino acid selected from the group consisting of R and G. In some embodiments, (BB)11is an amino acid selected from the group consisting of Q and L. In some embodiments, (BB)12 is an amino acid selected from the group consisting of D and A. In some embodiments, (BB)13 is an amino acid selected from the group consisting of A and P. In some embodiments, (BB)14is an ACTIVE / 131743364.1 117Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT amino acid selected from the group consisting of T and E. In some embodiments, (BB)15is an amino acid selected from the group consisting of A and M. In some embodiments, (BB)16is an amino acid selected from the group consisting of L and R. In some embodiments, (BB)17is an amino acid selected from the group consisting of P and G. In some embodiments, (BB)18is an amino acid selected from the group consisting of S and A. In some embodiments, (BB)19is an amino acid selected from the group consisting of M and G. In some embodiments, (BB)20is an amino acid selected from the group consisting of S and A. In some embodiments, (BB)21is an amino acid selected from the group consisting of S and A. In some embodiments, (BB)22 is an amino acid selected from the group consisting of T and G. In some embodiments, (BB)23is an amino acid selected from the group consisting of F and L. In some embodiments, (BB)24is an amino acid selected from the group consisting of W and L. In some embodiments, (BB)25is alanine (A). In some embodiments, (BB)26is an amino acid selected from the group consisting of F and L. In some embodiments, (BB)27is an amino acid selected from the group consisting of M and L. In some embodiments, (BB)28is an amino acid selected from the group consisting of I and L. In some embodiments, (BB)29is leucine (L). In some embodiments, (BB)30is an amino acid selected from the group consisting of A and L. In some embodiments, (BB)31is an amino acid selected from the group consisting of S and L. In some embodiments, (BB)32 is leucine (L). In some embodiments, (BB)33 is leucine (L). In some embodiments, (BB)34is an amino acid selected from the group consisting of I and L. In some embodiments, (BB)35is an amino acid selected from the group consisting of A and L. In some embodiments, (BB)36is an amino acid selected from the group consisting of Y and G. In some embodiments, (BB)37is an amino acid selected from the group consisting of C and L. In some embodiments, (BB)38is an amino acid selected from the group consisting of S and G. In some embodiments, (BB)39is an amino acid selected from the group consisting of Q and G. In some embodiments, (BB)40is an amino acid selected from the group consisting of L and R. In some embodiments, (BB)41is an amino acid selected from the group consisting of A and V. In some embodiments, (BB)42is an amino acid selected from the group consisting of A and E. In some embodiments, (BB)43 is glycine (G).

[0179] It is to be understood that a variant of SEQ ID NO: 28 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXVIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 2 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 3 of SEQ ID NO: 28. In some ACTIVE / 131743364.1 118Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 4 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 5 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 6 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 7 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 8 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 9 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 10 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 11 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 12 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 13 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 14 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 15 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 16 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 17 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 18 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 19 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 20 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 21 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 22 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 23 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 24 of SEQ ID NO: 28. In some embodiments, the signal peptide ACTIVE / 131743364.1 119Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 26 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 27 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 28 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 30 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 31 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 34 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 35 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 36 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 37 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 38 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 39 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 40 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 41 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at position 42 of SEQ ID NO: 28. The variant may also comprise any number of substitutions as provided by Formula XXVIII. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 27, 28, 30, 31, 34, 35, 36, 37, 38, 39, 40, 41, or 42 of SEQ ID NO: 28. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 28 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 27, 28, 30, 31, 34, 35, 36, 37, 38, 39, 40, 41, or 42 of SEQ ID NO: 28.

[0180] Variants of SEQ ID NO: 29 (Formula XXIX)

[0181] In some embodiments, the signal peptide comprises an amino acid sequence represented by: ACTIVE / 131743364.1 120Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT (CC)1-(CC)2-(CC)3-(CC)4-(CC)5-(CC)6-(CC)7-(CC)8-(CC)9-(CC)10-(CC)11-(CC)12-(CC)13- (CC)14-(CC)15-(CC)16-(CC)17-(CC)18-(CC)19-(CC)20-(CC)21-(CC)22-(CC)23-(CC)24-(CC)25- (CC)26-(CC)27-(CC)28-(CC)29-(CC)30-(CC)31-(CC)32-(CC)33-(CC)34-(CC)35-(CC)36-(CC)37- (CC)38-(CC)39-(CC)40-(CC)41-(CC)42-(CC)43-(CC)44-(CC)45-(CC)46-(CC)47(Formula XXIX); wherein the identity of each of (CC)1– (CC)47are as provided for in Table 30 below. Table 30ACTIVE / 131743364.1 121Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0182] In some embodiments, (CC)1is methionine (M). In some embodiments, (CC)2is an amino acid selected from the group consisting of E and H. In some embodiments, (CC)3is an amino acid selected from the group consisting of C, L, and K. In some embodiments, (CC)4is an amino acid selected from the group consisting of A, G, and E. In some embodiments, (CC)5 is an amino acid selected from the group consisting of L and A. In some embodiments, (CC)6is an amino acid selected from the group consisting of L, G, and E. In some embodiments, (CC)7is an amino acid selected from the group consisting of L, G, and M. In some embodiments, (CC)8is an amino acid selected from the group consisting of L and A. In some embodiments, (CC)9is an amino acid selected from the group consisting of C, S, and I. In ACTIVE / 131743364.1 122Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT some embodiments, (CC)10is an amino acid selected from the group consisting of A, T, and G. In some embodiments, (CC)11is an amino acid selected from the group consisting of F, L, and P. In some embodiments, (CC)12is an amino acid selected from the group consisting of P, S, and Q. In some embodiments, (CC)13is an amino acid selected from the group consisting of A, H, and L. In some embodiments, (CC)14is an amino acid selected from the group consisting of A, C, and D. In some embodiments, (CC)15is an amino acid selected from the group consisting of G, P, and E. In some embodiments, (CC)16is an amino acid selected from the group consisting of S, W, and K. In some embodiments, (CC)17 is an amino acid selected from the group consisting of G, P, and R. In some embodiments, (CC)18is an amino acid selected from the group consisting of P, R, and W. In some embodiments, (CC)19is an amino acid selected from the group consisting of P, R, and G. In some embodiments, (CC)20is an amino acid selected from the group consisting of R, Q, and W. In some embodiments, (CC)21is an amino acid selected from the group consisting of G, A, and R. In some embodiments, (CC)22is an amino acid selected from the group consisting of L and P. In some embodiments, (CC)23is an amino acid selected from the group consisting of A, L, and G. In some embodiments, (CC)24is an amino acid selected from the group consisting of G and D. In some embodiments, (CC)25is an amino acid selected from the group consisting of L and G. In some embodiments, (CC)26 is an amino acid selected from the group consisting of S and G. In some embodiments, (CC)27is an amino acid selected from the group consisting of A and R. In some embodiments, (CC)28is an amino acid selected from the group consisting of V, Q, and A. In some embodiments, (CC)29is an amino acid selected from the group consisting of P and A. In some embodiments, (CC)30is an amino acid selected from the group consisting of K, A, and P. In some embodiments, (CC)31is an amino acid selected from the group consisting of A, L, and F. In some embodiments, (CC)32is an amino acid selected from the group consisting of L and W. In some embodiments, (CC)33is an amino acid selected from the group consisting of P and Q. In some embodiments, (CC)34is an amino acid selected from the group consisting of L, T, and Q. In some embodiments, (CC)35is an amino acid selected from the group consisting of C, L, and A. In some embodiments, (CC)36 is an amino acid selected from the group consisting of C, A, and L. In some embodiments, (CC)37is an amino acid selected from the group consisting of L, A, and S. In some embodiments, (CC)38is an amino acid selected from the group consisting of C, L, and F. In some embodiments, (CC)39is an amino acid selected from the group consisting of C, A, and L. In some embodiments, (CC)40is an amino acid selected from the group consisting of L and A. In some embodiments, (CC)41is an amino acid selected from the group consisting of L and S. In some embodiments, (CC)42is an amino acid ACTIVE / 131743364.1 123Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT selected from the group consisting of V, S, and L. In some embodiments, (CC)43is an amino acid selected from the group consisting of A, S, and P. In some embodiments, (CC)44is an amino acid selected from the group consisting of A, V, and L. In some embodiments, (CC)45is alanine (A). In some embodiments, (CC)46is an amino acid selected from the group consisting of L, E, and S. In some embodiments, (CC)47is alanine (A).

[0183] It is to be understood that a variant of SEQ ID NO: 29 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXIX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 2 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 3 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 4 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 5 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 6 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 7 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 8 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 9 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 10 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 11 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 12 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 13 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 14 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 15 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 16 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 17 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino ACTIVE / 131743364.1 124Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT acid sequence of SEQ ID NO: 29 and a substitution at position 18 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 19 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 20 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 21 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 22 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 23 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 24 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 25 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 26 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 27 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 28 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 29 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 30 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 31 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 32 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 33 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 34 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 35 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 36 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 37 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 38 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a ACTIVE / 131743364.1 125Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution at position 39 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 40 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 41 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 42 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 43 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 44 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at position 46 of SEQ ID NO: 29. The variant may also comprise any number of substitutions as provided by Formula XXIX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at at least one position corresponding to position 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, or 46 of SEQ ID NO: 29. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 29 and a substitution at more than one position corresponding to position 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, or 46 of SEQ ID NO: 29.

[0184] Variants of SEQ ID NO: 30 (Formula XXX)

[0185] In some embodiments, the signal peptide comprises an amino acid sequence represented by: (DD)1-(DD)2-(DD)3-(DD)4-(DD)5-(DD)6-(DD)7-(DD)8-(DD)9-(DD)10-(DD)11-(DD)12-(DD)13- (DD)14-(DD)15-(DD)16-(DD)17-(DD)18-(DD)19-(DD)20-(DD)21-(DD)22-(DD)23-(DD)24-(DD)25- (DD)26-(DD)27-(DD)28-(DD)29-(DD)30-(DD)31-(DD)32-(DD)33-(DD)34-(DD)35-(DD)36-(DD)37- (DD)38-(DD)39-(DD)40-(DD)41-(DD)42-(DD)43-(DD)44-(DD)45-(DD)46-(DD)47-(DD)48(Formula XXX); wherein the identity of each of (DD)1– (DD)48are as provided for in Table 31 below. Table 31ACTIVE / 131743364.1 126Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENTACTIVE / 131743364.1 127Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0186] In some embodiments, (DD)1is methionine (M). In some embodiments, (DD)2is an amino acid selected from the group consisting of G and H. In some embodiments, (DD)3is an amino acid selected from the group consisting of K and P. In some embodiments, (DD)4is an amino acid selected from the group consisting of I and P. In some embodiments, (DD)5is an amino acid selected from the group consisting of S and K. In some embodiments, (DD)6is an amino acid selected from the group consisting of S and T. In some embodiments, (DD)7is an amino acid selected from the group consisting of L and P. In some embodiments, (DD)8is an amino acid selected from the group consisting of P and S. In some embodiments, (DD)9is an amino acid selected from the group consisting of T and G. In some embodiments, (DD)10 is an amino acid selected from the group consisting of Q and A. In some embodiments, (DD)11 is leucine (L). In some embodiments, (DD)12is an amino acid selected from the group consisting of F and H. In some embodiments, (DD)13is an amino acid selected from the group consisting of K and R. In some embodiments, (DD)14is an amino acid selected from the group consisting of C and K. In some embodiments, (DD)15is an amino acid selected from the group consisting of C and R. In some embodiments, (DD)16is an amino acid selected from the group consisting of F and K. In some embodiments, (DD)17is an amino acid selected from the group consisting ACTIVE / 131743364.1 128Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT of C and M. In some embodiments, (DD)18is an amino acid selected from the group consisting of D and A. In some embodiments, (DD)19is an amino acid selected from the group consisting of F and A. In some embodiments, (DD)20is an amino acid selected from the group consisting of L and W. In some embodiments, (DD)21is an amino acid selected from the group consisting of K and P. In some embodiments, (DD)22is an amino acid selected from the group consisting of V and F. In some embodiments, (DD)23is an amino acid selected from the group consisting of K and S. In some embodiments, (DD)24is an amino acid selected from the group consisting of M and R. In some embodiments, (DD)25 is an amino acid selected from the group consisting of H and L. In some embodiments, (DD)26is an amino acid selected from the group consisting of T and W. In some embodiments, (DD)27is an amino acid selected from the group consisting of M and K. In some embodiments, (DD)28is an amino acid selected from the group consisting of S and V. In some embodiments, (DD)29is serine (S). In some embodiments, (DD)30is an amino acid selected from the group consisting of S and D. In some embodiments, (DD)31is an amino acid selected from the group consisting of H and P. In some embodiments, (DD)32is an amino acid selected from the group consisting of L and I. In some embodiments, (DD)33is an amino acid selected from the group consisting of F and L. In some embodiments, (DD)34is an amino acid selected from the group consisting of Y and F. In some embodiments, (DD)35is an amino acid selected from the group consisting of L and Q. In some embodiments, (DD)36 is an amino acid selected from the group consisting of A and M. In some embodiments, (DD)37is an amino acid selected from the group consisting of L and T. In some embodiments, (DD)38is an amino acid selected from the group consisting of C and L. In some embodiments, (DD)39is an amino acid selected from the group consisting of L and I. In some embodiments, (DD)40is an amino acid selected from the group consisting of L and A. In some embodiments, (DD)41is an amino acid selected from the group consisting of T and A. In some embodiments, (DD)42is an amino acid selected from the group consisting of F and L. In some embodiments, (DD)43is an amino acid selected from the group consisting of T and L. In some embodiments, (DD)44is an amino acid selected from the group consisting of S and P. In some embodiments, (DD)45is an amino acid selected from the group consisting of S and A. In some embodiments, (DD)46 is an amino acid selected from the group consisting of A and V. In some embodiments, (DD)47is an amino acid selected from the group consisting of T and L. In some embodiments, (DD)48is an amino acid selected from the group consisting of A and G.

[0187] It is to be understood that a variant of SEQ ID NO: 30 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXX. Accordingly, in some embodiments, the ACTIVE / 131743364.1 129Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 2 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 3 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 4 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 5 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 6 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 7 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 8 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 9 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 10 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 12 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 13 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 14 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 15 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 16 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 17 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 18 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 19 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 20 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 21 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 22 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 23 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino ACTIVE / 131743364.1 130Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT acid sequence of SEQ ID NO: 30 and a substitution at position 24 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 25 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 26 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 27 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 28 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 30 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 31 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 32 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 33 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 34 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 35 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 36 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 37 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 38 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 39 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 40 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 41 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 42 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 43 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 44 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 45 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a ACTIVE / 131743364.1 131Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT substitution at position 46 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 47 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at position 48 of SEQ ID NO: 30. The variant may also comprise any number of substitutions as provided by Formula XXX. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at at least one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 of SEQ ID NO: 30. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 30 and a substitution at more than one position corresponding to position 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, or 48 of SEQ ID NO: 30.

[0188] Variants of SEQ ID NO: 31 (Formula XXXI)

[0189] In some embodiments, the signal peptide comprises an amino acid sequence represented by: (EE)1-(EE)2-(EE)3-(EE)4-(EE)5-(EE)6-(EE)7-(EE)8-(EE)9-(EE)10-(EE)11-(EE)12-(EE)13-(EE)14- (EE)15-(EE)16-(EE)17-(EE)18-(EE)19-(EE)20-(EE)21-(EE)22-(EE)23-(EE)24-(EE)25-(EE)26-(EE)27- (EE)28-(EE)29-(EE)30-(EE)31-(EE)32-(EE)33-(EE)34-(EE)35-(EE)36-(EE)37-(EE)38-(EE)39-(EE)40- (EE)41-(EE)42-(EE)43-(EE)44-(EE)45-(EE)46-(EE)47-(EE)48-(EE)49(Formula XXXI); wherein the identity of each of (EE)1– (EE)49are as provided for in Table 32 below. Table 32ACTIVE / 131743364.1 132Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENTACTIVE / 131743364.1 133Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT

[0190] In some embodiments, (EE)1is methionine (M). In some embodiments, (EE)2is an amino acid selected from the group consisting of A, Q, and Y. In some embodiments, (EE)3is an amino acid selected from the group consisting of P, R, and K. In some embodiments, (EE)4is an amino acid selected from the group consisting of A and R. In some embodiments, (EE)5is an amino acid selected from the group consisting of G, V, and R. In some embodiments, (EE)6 is an amino acid selected from the group consisting of P and C. In some embodiments, (EE)7is an amino acid selected from the group consisting of A, E, and P. In some embodiments, (EE)8is an amino acid selected from the group consisting of G and A. In some embodiments, (EE)9is an amino acid selected from the group consisting of H, F, and G. In some embodiments, (EE)10is an amino acid selected from the group consisting of P, G, and S. In some embodiments, (EE)11is an amino acid selected from the group consisting of P, R, and G. In some embodiments, (EE)12is an amino acid selected from the group consisting of P, R, and G. In some embodiments, (EE)13is an amino acid selected from the group consisting of P and K. In some embodiments, (EE)14is an amino acid selected from the group consisting of S, L, and G. In some embodiments, (EE)15 is an amino acid selected from the group consisting of P, G, and A. In some embodiments, (EE)16 is an amino acid selected from the group consisting of Q, S, and E. In some embodiments, (EE)17is an amino acid selected from the group consisting of A, D, and P. In some embodiments, (EE)18is an amino acid selected from the group consisting of C, M, and P. In some embodiments, (EE)19is an amino acid selected from the group consisting of V, G, and A. In some embodiments, (EE)20is an amino acid selected from the group consisting of C, N, and M. In some embodiments, (EE)21is an amino acid selected from the group consisting of A and P. In some embodiments, (EE)22is an amino ACTIVE / 131743364.1 134Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT acid selected from the group consisting of G, E, and A. In some embodiments, (EE)23is an amino acid selected from the group consisting of K, R, and P. In some embodiments, (EE)24is an amino acid selected from the group consisting of M, A, and R. In some embodiments, (EE)25is an amino acid selected from the group consisting of L, P, and G. In some embodiments, (EE)26is an amino acid selected from the group consisting of A, G, and R. In some embodiments, (EE)27is an amino acid selected from the group consisting of M, S, and A. In some embodiments, (EE)28is an amino acid selected from the group consisting of G, R, and A. In some embodiments, (EE)29 is an amino acid selected from the group consisting of A, S, and P. In some embodiments, (EE)30is an amino acid selected from the group consisting of L, F, and W. In some embodiments, (EE)31is an amino acid selected from the group consisting of A, G, and T. In some embodiments, (EE)32is an amino acid selected from the group consisting of G, P, and T. In some embodiments, (EE)33is an amino acid selected from the group consisting of F, V, and A. In some embodiments, (EE)34is an amino acid selected from the group consisting of W, P, and L. In some embodiments, (EE)35is an amino acid selected from the group consisting of I, T, and L. In some embodiments, (EE)36is leucine (L). In some embodiments, (EE)37is an amino acid selected from the group consisting of L and C. In some embodiments, (EE)38is leucine (L). In some embodiments, (EE)39is an amino acid selected from the group consisting of L and A. In some embodiments, (EE)40 is an amino acid selected from the group consisting of T, A, and S. In some embodiments, (EE)41is an amino acid selected from the group consisting of Y, A, and Q. In some embodiments, (EE)42is an amino acid selected from the group consisting of G, A, and V. In some embodiments, (EE)43is an amino acid selected from the group consisting of L and Y. In some embodiments, (EE)44is an amino acid selected from the group consisting of L and S. In some embodiments, (EE)45is an amino acid selected from the group consisting of S, A, and P. In some embodiments, (EE)46is an amino acid selected from the group consisting of W, V, and G. In some embodiments, (EE)47is an amino acid selected from the group consisting of S and G. In some embodiments, (EE)48is an amino acid selected from the group consisting of Q, D, and C. In some embodiments, (EE)49 is alanine (A).

[0191] It is to be understood that a variant of SEQ ID NO: 31 is not required to comprise a substitution at each position where a substitution is provided, but rather need only contain one substitution to be within the scope of Formula XXXI. Accordingly, in some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 31 and a substitution at position 2 of SEQ ID NO: 31. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 31 and a substitution at position 3 of SEQ ID NO: 31. In some ACTIVE / 131743364.1 135Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 31 and a substitution at position 4 of SEQ ID NO: 31. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 31 and a substitution at position 5 of SEQ ID NO: 31. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 31 and a substitution at position 6 of SEQ ID NO: 31. In some embodiments, the signal peptide comprises the amino acid sequence of SEQ ID NO: 31 and a substitution at position 7 of ...

Claims

Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT CLAIMS What is claimed is:

1. A signal peptide comprising an amino acid sequence selected from the group consisting of Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, XIII, XIV, XV, XVI, XVII, XVIII, XIX. XX, XXI, XXII, XXIII, XXIV, XXV, XXVI, XXVII, XXVIII, XXIX, XXX, XXXI, XXXII, or XXXIII; wherein Formula I is represented as: A1-A2-A3-A4-A5(Formula I) and the identities of A1-A5are as provided in Table 2; wherein Formula II is represented as: B1-B2-B3-B4-B5-B6-B7-B8-B9-B10-B11-B12-B13-B14-B15(Formula II) and the identities of B1-B15are as provided in Table 3; wherein Formula III is represented as: C1-C2-C3-C4-C5-C6-C7-C8-C9-C10-C11-C12-C13-C14-C15-C16(Formula III) and the identities of C1-C16are as provided in Table 4; wherein Formula IV is represented as: D1-D2-D3-D4-D5-D6-D7-D8-D9-D10-D11-D12-D13-D14-D15-D16-D17 (Formula IV) and the identities of D1-D17are as provided in Table 5; wherein Formula V is represented as: E1-E2-E3-E4-E5-E6-E7-E8-E9-E10-E11-E12-E13-E14-E15-E16-E17-E18(Formula V) and the identities of E1-E18are as provided in Table 6; wherein Formula VI is represented as: F1-F2-F3-F4-F5-F6-F7-F8-F9-F10-F11-F12-F13-F14-F15-F16-F17-F18-F19(Formula VI) and the identities of F1-F19are as provided in Table 7; wherein Formula VII is represented as: G1-G2-G3-G4-G5-G6-G7-G8-G9-G10-G11-G12-G13-G14-G15-G16-G17-G18-G19-G20(Formula VII) and the identities of G1-G20 are as provided in Table 8; wherein Formula VIII is represented as: H1-H2-H3-H4-H5-H6-H7-H8-H9-H10-H11-H12-H13-H14-H15-H16-H17-H18-H19-H20-H21(Formula VIII) and the identities of H1-H21are as provided in Table 9; wherein Formula IX is represented as: I1-I2-I3-I4-I5-I6-I7-I8-I9-I10-I11-I12-I13-I14-I15-I16-I17-I18-I19-I20-I21-I22(Formula IX) ACTIVE / 131743364.1 179Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT and the identities of I1-I22are as provided in Table 10; wherein Formula X is represented as: J1-J2-J3-J4-J5-J6-J7-J8-J9-J10-J11-J12-J13-J14-J15-J16-J17-J18-J19-J20-J21-J22-J23(Formula X) and the identities of J1-J23are as provided in Table 11; wherein Formula XI is represented as: K1-K2-K3-K4-K5-K6-K7-K8-K9-K10-K11-K12-K13-K14-K15-K16-K17-K18-K19-K20-K21-K22-K23- K24(Formula XI) and the identities of K1-K24 are as provided in Table 12; wherein Formula XII is represented as: L1-L2-L3-L4-L5-L6-L7-L8-L9-L10-L11-L12-L13-L14-L15-L16-L17-L18-L19-L20-L21-L22-L23-L24-L25(Formula XII) and the identities of L1-L25are as provided in Table 13; wherein Formula XIII is represented as: M1-M2-M3-M4-M5-M6-M7-M8-M9-M10-M11-M12-M13-M14-M15-M16-M17-M18-M19-M20-M21- M22-M23-M24-M25-M26(Formula XIII) and the identities of M1-M26are as provided in Table 14; wherein Formula XIV is represented as: N1-N2-N3-N4-N5-N6-N7-N8-N9-N10-N11-N12-N13-N14-N15-N16-N17-N18-N19-N20-N21-N22-N23- N24-N25-N26-N27(Formula XIV) and the identities of N1-N27are as provided in Table 15; wherein Formula XV is represented as: O1-O2-O3-O4-O5-O6-O7-O8-O9-O10-O11-O12-O13-O14-O15-O16-O17-O18-O19-O20-O21-O22-O23- O24-O25-O26-O27-O28(Formula XV) and the identities of O1-O28are as provided in Table 16; wherein Formula XVI is represented as: P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-P15-P16-P17-P18-P19-P20-P21-P22-P23-P24-P25-P26- P27-P28-P29(Formula XVI) and the identities of P1-P29 are as provided in Table 17; wherein Formula XVII is represented as: Q1-Q2-Q3-Q4-Q5-Q6-Q7-Q8-Q9-Q10-Q11-Q12-Q13-Q14-Q15-Q16-Q17-Q18-Q19-Q20-Q21-Q22-Q23- Q24-Q25-Q26-Q27-Q28-Q29-Q30(Formula XVII) and the identities of Q1-Q30are as provided in Table 18; wherein Formula XVIII is represented as: ACTIVE / 131743364.1 180Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT R1-R2-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-R17-R18-R19-R20-R21-R22-R23-R24- R25-R26-R27-R28-R29-R30-R31(Formula XVIII) and the identities of R1-R31are as provided in Table 19; wherein Formula XIX is represented as: S1-S2-S3-S4-S5-S6-S7-S8-S9-S10-S11-S12-S13-S14-S15-S16-S17-S18-S19-S20-S21-S22-S23-S24-S25-S26- S27-S28-S29-S30-S31-S32(Formula XIX) and the identities of S1-S32are as provided in Table 20; wherein Formula XX is represented as: T1-T2-T3-T4-T5-T6-T7-T8-T9-T10-T11-T12-T13-T14-T15-T16-T17-T18-T19-T20-T21-T22-T23-T24-T25- T26-T27-T28-T29-T30-T31-T32-T33(Formula XX) and the identities of T1-T33are as provided in Table 21; wherein Formula XXI is represented as: U1-U2-U3-U4-U5-U6-U7-U8-U9-U10-U11-U12-U13-U14-U15-U16-U17-U18-U19-U20-U21-U22-U23- U24-U25-U26-U27-U28-U29-U30-U31-U32-U33-U34(Formula XXI) and the identities of U1-U34are as provided in Table 22; wherein Formula XXII is represented as: V1-V2-V3-V4-V5-V6-V7-V8-V9-V10-V11-V12-V13-V14-V15-V16-V17-V18-V19-V20-V21-V22-V23- V24-V25-V26-V27-V28-V29-V30-V31-V32-V33-V34-V35 (Formula XXII) and the identities of V1-V35are as provided in Table 23; wherein Formula XXIII is represented as: W1-W2-W3-W4-W5-W6-W7-W8-W9-W10-W11-W12-W13-W14-W15-W16-W17-W18-W19-W20- W21-W22-W23-W24-W25-W26-W27-W28-W29-W30-W31-W32-W33-W34-W35-W36(Formula XXIII) and the identities of W1-W36are as provided in Table 24; wherein Formula XXIV is represented as: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-X23- X24-X25-X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37(Formula XXIV) and the identities of X1-X37 are as provided in Table 25; wherein Formula XXV is represented as: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15-Y16-Y17-Y18-Y19-Y20-Y21-Y22-Y23- Y24-Y25-Y26-Y27-Y28-Y29-Y30-Y31-Y32-Y33-Y34-Y35-Y36-Y37-Y38(Formula XXV) and the identities of Y1-Y38are as provided in Table 26; wherein Formula XXVI is represented as: ACTIVE / 131743364.1 181Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT Z1-Z2-Z3-Z4-Z5-Z6-Z7-Z8-Z9-Z10-Z11-Z12-Z13-Z14-Z15-Z16-Z17-Z18-Z19-Z20-Z21-Z22-Z23-Z24-Z25- Z26-Z27-Z28-Z29-Z30-Z31-Z32-Z33-Z34-Z35-Z36-Z37-Z38-Z39(Formula XXVI) and the identities of Z1-Z39are as provided in Table 27; wherein Formula XXVII is represented as: (AA)1-(AA)2-(AA)3-(AA)4-(AA)5-(AA)6-(AA)7-(AA)8-(AA)9-(AA)10-(AA)11-(AA)12-(AA)13- (AA)14-(AA)15-(AA)16-(AA)17-(AA)18-(AA)19-(AA)20-(AA)21-(AA)22-(AA)23-(AA)24-(AA)25- (AA)26-(AA)27-(AA)28-(AA)29-(AA)30-(AA)31-(AA)32-(AA)33-(AA)34-(AA)35-(AA)36-(AA)37- (AA)38-(AA)39-(AA)40-(AA)41 (Formula XXVII) and the identities of (AA)1-(AA)41are as provided in Table 28; wherein Formula XXVIII is represented as: (BB)1-(BB)2-(BB)3-(BB)4-(BB)5-(BB)6-(BB)7-(BB)8-(BB)9-(BB)10-(BB)11-(BB)12-(BB)13- (BB)14-(BB)15-(BB)16-(BB)17-(BB)18-(BB)19-(BB)20-(BB)21-(BB)22-(BB)23-(BB)24-(BB)25- (BB)26-(BB)27-(BB)28-(BB)29-(BB)30-(BB)31-(BB)32-(BB)33-(BB)34-(BB)35-(BB)36-(BB)37- (BB)38-(BB)39-(BB)40-(BB)41-(BB)42-(BB)43(Formula XXVIII) and the identities of (BB)1-(BB)43are as provided in Table 29; wherein Formula XXIX is represented as: (CC)1-(CC)2-(CC)3-(CC)4-(CC)5-(CC)6-(CC)7-(CC)8-(CC)9-(CC)10-(CC)11-(CC)12-(CC)13- (CC)14-(CC)15-(CC)16-(CC)17-(CC)18-(CC)19-(CC)20-(CC)21-(CC)22-(CC)23-(CC)24-(CC)25- (CC)26-(CC)27-(CC)28-(CC)29-(CC)30-(CC)31-(CC)32-(CC)33-(CC)34-(CC)35-(CC)36-(CC)37- (CC)38-(CC)39-(CC)40-(CC)41-(CC)42-(CC)43-(CC)44-(CC)45-(CC)46-(CC)47(Formula XXIX) and the identities of (CC)1-(CC)47are as provided in Table 30; wherein Formula XXX is represented as: (DD)1-(DD)2-(DD)3-(DD)4-(DD)5-(DD)6-(DD)7-(DD)8-(DD)9-(DD)10-(DD)11-(DD)12-(DD)13- (DD)14-(DD)15-(DD)16-(DD)17-(DD)18-(DD)19-(DD)20-(DD)21-(DD)22-(DD)23-(DD)24-(DD)25- (DD)26-(DD)27-(DD)28-(DD)29-(DD)30-(DD)31-(DD)32-(DD)33-(DD)34-(DD)35-(DD)36-(DD)37- (DD)38-(DD)39-(DD)40-(DD)41-(DD)42-(DD)43-(DD)44-(DD)45-(DD)46-(DD)47-(DD)48(Formula XXX) and the identities of (DD)1-(DD)48 are as provided in Table 31; wherein Formula XXXI is represented as: (EE)1-(EE)2-(EE)3-(EE)4-(EE)5-(EE)6-(EE)7-(EE)8-(EE)9-(EE)10-(EE)11-(EE)12-(EE)13-(EE)14- (EE)15-(EE)16-(EE)17-(EE)18-(EE)19-(EE)20-(EE)21-(EE)22-(EE)23-(EE)24-(EE)25-(EE)26-(EE)27- (EE)28-(EE)29-(EE)30-(EE)31-(EE)32-(EE)33-(EE)34-(EE)35-(EE)36-(EE)37-(EE)38-(EE)39-(EE)40- (EE)41-(EE)42-(EE)43-(EE)44-(EE)45-(EE)46-(EE)47-(EE)48-(EE)49(Formula XXXI) and the identities of (EE)1-(EE)49are as provided in Table 32; ACTIVE / 131743364.1 182Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT wherein Formula XXXII is represented as: (FF)1-(FF)2-(FF)3-(FF)4-(FF)5-(FF)6-(FF)7-(FF)8-(FF)9-(FF)10-(FF)11-(FF)12-(FF)13-(FF)14- (FF)15-(FF)16-(FF)17-(FF)18-(FF)19-(FF)20-(FF)21-(FF)22-(FF)23-(FF)24-(FF)25-(FF)26-(FF)27- (FF)28-(FF)29-(FF)30-(FF)31-(FF)32-(FF)33-(FF)34-(FF)35-(FF)36-(FF)37-(FF)38-(FF)39-(FF)40- (FF)41-(FF)42-(FF)43-(FF)44-(FF)45-(FF)46-(FF)47-(FF)48-(FF)49-(FF)50(Formula XXXII) and the identities of (FF)1-(FF)50are as provided in Table 33; and wherein Formula XXXIII is represented as: (GG)1-(GG)2-(GG)3-(GG)4-(GG)5-(GG)6-(GG)7-(GG)8-(GG)9-(GG)10-(GG)11-(GG)12-(GG)13- (GG)14-(GG)15-(GG)16-(GG)17-(GG)18-(GG)19-(GG)20-(GG)21-(GG)22-(GG)23-(GG)24-(GG)25- (GG)26-(GG)27-(GG)28-(GG)29-(GG)30-(GG)31-(GG)32-(GG)33-(GG)34-(GG)35-(GG)36-(GG)37- (GG)38-(GG)39-(GG)40-(GG)41-(GG)42-(GG)43-(GG)44-(GG)45-(GG)46-(GG)47-(GG)48-(GG)49- (GG)50-(GG)51(Formula XXXIII) and the identities of (GG)1-(GG)51are as provided in Table 34.

2. The signal peptide of claim 1, comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 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, or 33.

3. A signal peptide comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 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, or 33.

4. The signal peptide of any one of claims 1-3, wherein the signal peptide is a novel signal peptide.

5. A recombinant polypeptide comprising a formula of X1-(Y1)a-Z1, wherein: X1is a signal peptide, Y1is a peptide linker, and Z1is a payload protein, wherein a is an integer selected from 0 and 1. ACTIVE / 131743364.1 183Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT 6. The recombinant polypeptide of claim 5, wherein X1comprises an amino acid sequence selected from the group consisting of Formula I, II, III, IV, V, VI, VII, VIII, IX, X, XI, and XII; wherein Formula I is represented as: A1-A2-A3-A4-A5-A6-A7-A8-A9-A10-A11-A12-A13-A14-A15(Formula I) and the identities of A1-A15are as provided in Table 2; wherein Formula II is represented as: B1-B2-B3-B4-B5-B6-B7-B8-B9-B10-B11-B12-B13-B14-B15-B16(Formula II) and the identities of B1-B16are as provided in Table 3; wherein Formula III is represented as: C1-C2-C3-C4-C5-C6-C7-C8-C9-C10-C11-C12-C13-C14-C15-C16-C17(Formula III) and the identities of C1-C17are as provided in Table 4; wherein Formula IV is represented as: D1-D2-D3-D4-D5-D6-D7-D8-D9-D10-D11-D12-D13-D14-D15-D16-D17-D18(Formula IV) and the identities of D1-D18are as provided in Table 5; wherein Formula V is represented as: E1-E2-E3-E4-E5-E6-E7-E8-E9-E10-E11-E12-E13-E14-E15-E16-E17-E18-E19 (Formula V) and the identities of E1-E19are as provided in Table 6; wherein Formula VI is represented as: F1-F2-F3-F4-F5-F6-F7-F8-F9-F10-F11-F12-F13-F14-F15-F16-F17-F18-F19-F20(Formula VI) and the identities of F1-F20are as provided in Table 7; wherein Formula VII is represented as: G1-G2-G3-G4-G5-G6-G7-G8-G9-G10-G11-G12-G13-G14-G15-G16-G17-G18-G19-G20-G21(Formula VII) and the identities of G1-G21are as provided in Table 8; wherein Formula VIII is represented as: H1-H2-H3-H4-H5-H6-H7-H8-H9-H10-H11-H12-H13-H14-H15-H16-H17-H18-H19-H20-H21-H22 (Formula VIII) and the identities of H1-H22are as provided in Table 9; wherein Formula IX is represented as: I1-I2-I3-I4-I5-I6-I7-I8-I9-I10-I11-I12-I13-I14-I15-I16-I17-I18-I19-I20-I21-I22-I23(Formula IX) and the identities of I1-I23are as provided in Table 10; wherein Formula X is represented as: ACTIVE / 131743364.1 184Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT J1-J2-J3-J4-J5-J6-J7-J8-J9-J10-J11-J12-J13-J14-J15-J16-J17-J18-J19-J20-J21-J22-J23-J24(Formula X) and the identities of J1-J24are as provided in Table 11; wherein Formula XI is represented as: K1-K2-K3-K4-K5-K6-K7-K8-K9-K10-K11-K12-K13-K14-K15-K16-K17-K18-K19-K20-K21-K22-K23- K24(Formula XI) and the identities of K1-K24are as provided in Table 12; wherein Formula XII is represented as: L1-L2-L3-L4-L5-L6-L7-L8-L9-L10-L11-L12-L13-L14-L15-L16-L17-L18-L19-L20-L21-L22-L23-L24-L25 (Formula XII) and the identities of L1-L25are as provided in Table 13; wherein Formula XIII is represented as: M1-M2-M3-M4-M5-M6-M7-M8-M9-M10-M11-M12-M13-M14-M15-M16-M17-M18-M19-M20-M21- M22-M23-M24-M25-M26(Formula XIII) and the identities of M1-M26are as provided in Table 14; wherein Formula XIV is represented as: N1-N2-N3-N4-N5-N6-N7-N8-N9-N10-N11-N12-N13-N14-N15-N16-N17-N18-N19-N20-N21-N22-N23- N24-N25-N26-N27(Formula XIV) and the identities of N1-N27 are as provided in Table 15; wherein Formula XV is represented as: O1-O2-O3-O4-O5-O6-O7-O8-O9-O10-O11-O12-O13-O14-O15-O16-O17-O18-O19-O20-O21-O22-O23- O24-O25-O26-O27-O28(Formula XV) and the identities of O1-O28are as provided in Table 16; wherein Formula XVI is represented as: P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-P13-P14-P15-P16-P17-P18-P19-P20-P21-P22-P23-P24-P25-P26- P27-P28-P29(Formula XVI) and the identities of P1-P29are as provided in Table 17; wherein Formula XVII is represented as: Q1-Q2-Q3-Q4-Q5-Q6-Q7-Q8-Q9-Q10-Q11-Q12-Q13-Q14-Q15-Q16-Q17-Q18-Q19-Q20-Q21-Q22-Q23- Q24-Q25-Q26-Q27-Q28-Q29-Q30(Formula XVII) and the identities of Q1-Q30are as provided in Table 18; wherein Formula XVIII is represented as: R1-R2-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-R15-R16-R17-R18-R19-R20-R21-R22-R23-R24- R25-R26-R27-R28-R29-R30-R31(Formula XVIII) and the identities of R1-R31are as provided in Table 19; ACTIVE / 131743364.1 185Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT wherein Formula XIX is represented as: S1-S2-S3-S4-S5-S6-S7-S8-S9-S10-S11-S12-S13-S14-S15-S16-S17-S18-S19-S20-S21-S22-S23-S24-S25-S26- S27-S28-S29-S30-S31-S32(Formula XIX) and the identities of S1-S32are as provided in Table 20; wherein Formula XX is represented as: T1-T2-T3-T4-T5-T6-T7-T8-T9-T10-T11-T12-T13-T14-T15-T16-T17-T18-T19-T20-T21-T22-T23-T24-T25- T26-T27-T28-T29-T30-T31-T32-T33(Formula XX) and the identities of T1-T33 are as provided in Table 21; wherein Formula XXI is represented as: U1-U2-U3-U4-U5-U6-U7-U8-U9-U10-U11-U12-U13-U14-U15-U16-U17-U18-U19-U20-U21-U22-U23- U24-U25-U26-U27-U28-U29-U30-U31-U32-U33-U34(Formula XXI) and the identities of U1-U34are as provided in Table 22; wherein Formula XXII is represented as: V1-V2-V3-V4-V5-V6-V7-V8-V9-V10-V11-V12-V13-V14-V15-V16-V17-V18-V19-V20-V21-V22-V23- V24-V25-V26-V27-V28-V29-V30-V31-V32-V33-V34-V35(Formula XXII) and the identities of V1-V35are as provided in Table 23; wherein Formula XXIII is represented as: W1-W2-W3-W4-W5-W6-W7-W8-W9-W10-W11-W12-W13-W14-W15-W16-W17-W18-W19-W20- W21-W22-W23-W24-W25-W26-W27-W28-W29-W30-W31-W32-W33-W34-W35-W36(Formula XXIII) and the identities of W1-W36are as provided in Table 24; wherein Formula XXIV is represented as: X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-X15-X16-X17-X18-X19-X20-X21-X22-X23- X24-X25-X26-X27-X28-X29-X30-X31-X32-X33-X34-X35-X36-X37(Formula XXIV) and the identities of X1-X37are as provided in Table 25; wherein Formula XXV is represented as: Y1-Y2-Y3-Y4-Y5-Y6-Y7-Y8-Y9-Y10-Y11-Y12-Y13-Y14-Y15-Y16-Y17-Y18-Y19-Y20-Y21-Y22-Y23- Y24-Y25-Y26-Y27-Y28-Y29-Y30-Y31-Y32-Y33-Y34-Y35-Y36-Y37-Y38 (Formula XXV) and the identities of Y1-Y38are as provided in Table 26; wherein Formula XXVI is represented as: Z1-Z2-Z3-Z4-Z5-Z6-Z7-Z8-Z9-Z10-Z11-Z12-Z13-Z14-Z15-Z16-Z17-Z18-Z19-Z20-Z21-Z22-Z23-Z24-Z25- Z26-Z27-Z28-Z29-Z30-Z31-Z32-Z33-Z34-Z35-Z36-Z37-Z38-Z39(Formula XXVI) and the identities of Z1-Z39are as provided in Table 27; wherein Formula XXVII is represented as: ACTIVE / 131743364.1 186Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT (AA)1-(AA)2-(AA)3-(AA)4-(AA)5-(AA)6-(AA)7-(AA)8-(AA)9-(AA)10-(AA)11-(AA)12-(AA)13- (AA)14-(AA)15-(AA)16-(AA)17-(AA)18-(AA)19-(AA)20-(AA)21-(AA)22-(AA)23-(AA)24-(AA)25- (AA)26-(AA)27-(AA)28-(AA)29-(AA)30-(AA)31-(AA)32-(AA)33-(AA)34-(AA)35-(AA)36-(AA)37- (AA)38-(AA)39-(AA)40-(AA)41(Formula XXVII) and the identities of (AA)1-(AA)41are as provided in Table 28; wherein Formula XXVIII is represented as: (BB)1-(BB)2-(BB)3-(BB)4-(BB)5-(BB)6-(BB)7-(BB)8-(BB)9-(BB)10-(BB)11-(BB)12-(BB)13- (BB)14-(BB)15-(BB)16-(BB)17-(BB)18-(BB)19-(BB)20-(BB)21-(BB)22-(BB)23-(BB)24-(BB)25- (BB)26-(BB)27-(BB)28-(BB)29-(BB)30-(BB)31-(BB)32-(BB)33-(BB)34-(BB)35-(BB)36-(BB)37- (BB)38-(BB)39-(BB)40-(BB)41-(BB)42-(BB)43(Formula XXVIII) and the identities of (BB)1-(BB)43are as provided in Table 29; wherein Formula XXIX is represented as: (CC)1-(CC)2-(CC)3-(CC)4-(CC)5-(CC)6-(CC)7-(CC)8-(CC)9-(CC)10-(CC)11-(CC)12-(CC)13- (CC)14-(CC)15-(CC)16-(CC)17-(CC)18-(CC)19-(CC)20-(CC)21-(CC)22-(CC)23-(CC)24-(CC)25- (CC)26-(CC)27-(CC)28-(CC)29-(CC)30-(CC)31-(CC)32-(CC)33-(CC)34-(CC)35-(CC)36-(CC)37- (CC)38-(CC)39-(CC)40-(CC)41-(CC)42-(CC)43-(CC)44-(CC)45-(CC)46-(CC)47(Formula XXIX) and the identities of (CC)1-(CC)47are as provided in Table 30; wherein Formula XXX is represented as: (DD)1-(DD)2-(DD)3-(DD)4-(DD)5-(DD)6-(DD)7-(DD)8-(DD)9-(DD)10-(DD)11-(DD)12-(DD)13- (DD)14-(DD)15-(DD)16-(DD)17-(DD)18-(DD)19-(DD)20-(DD)21-(DD)22-(DD)23-(DD)24-(DD)25- (DD)26-(DD)27-(DD)28-(DD)29-(DD)30-(DD)31-(DD)32-(DD)33-(DD)34-(DD)35-(DD)36-(DD)37- (DD)38-(DD)39-(DD)40-(DD)41-(DD)42-(DD)43-(DD)44-(DD)45-(DD)46-(DD)47-(DD)48(Formula XXX) and the identities of (DD)1-(DD)48are as provided in Table 31; wherein Formula XXXI is represented as: (EE)1-(EE)2-(EE)3-(EE)4-(EE)5-(EE)6-(EE)7-(EE)8-(EE)9-(EE)10-(EE)11-(EE)12-(EE)13-(EE)14- (EE)15-(EE)16-(EE)17-(EE)18-(EE)19-(EE)20-(EE)21-(EE)22-(EE)23-(EE)24-(EE)25-(EE)26-(EE)27- (EE)28-(EE)29-(EE)30-(EE)31-(EE)32-(EE)33-(EE)34-(EE)35-(EE)36-(EE)37-(EE)38-(EE)39-(EE)40- (EE)41-(EE)42-(EE)43-(EE)44-(EE)45-(EE)46-(EE)47-(EE)48-(EE)49(Formula XXXI) and the identities of (EE)1-(EE)49are as provided in Table 32; wherein Formula XXXII is represented as: (FF)1-(FF)2-(FF)3-(FF)4-(FF)5-(FF)6-(FF)7-(FF)8-(FF)9-(FF)10-(FF)11-(FF)12-(FF)13-(FF)14- (FF)15-(FF)16-(FF)17-(FF)18-(FF)19-(FF)20-(FF)21-(FF)22-(FF)23-(FF)24-(FF)25-(FF)26-(FF)27- ACTIVE / 131743364.1 187Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT (FF)28-(FF)29-(FF)30-(FF)31-(FF)32-(FF)33-(FF)34-(FF)35-(FF)36-(FF)37-(FF)38-(FF)39-(FF)40- (FF)41-(FF)42-(FF)43-(FF)44-(FF)45-(FF)46-(FF)47-(FF)48-(FF)49-(FF)50(Formula XXXII) and the identities of (FF)1-(FF)50are as provided in Table 33; and wherein Formula XXXIII is represented as: (GG)1-(GG)2-(GG)3-(GG)4-(GG)5-(GG)6-(GG)7-(GG)8-(GG)9-(GG)10-(GG)11-(GG)12-(GG)13- (GG)14-(GG)15-(GG)16-(GG)17-(GG)18-(GG)19-(GG)20-(GG)21-(GG)22-(GG)23-(GG)24-(GG)25- (GG)26-(GG)27-(GG)28-(GG)29-(GG)30-(GG)31-(GG)32-(GG)33-(GG)34-(GG)35-(GG)36-(GG)37- (GG)38-(GG)39-(GG)40-(GG)41-(GG)42-(GG)43-(GG)44-(GG)45-(GG)46-(GG)47-(GG)48-(GG)49- (GG)50-(GG)51(Formula XXXIII) and the identities of (GG)1-(GG)51are as provided in Table 34.

7. The recombinant polypeptide of claim 5 or claim 6, wherein X1comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NO: 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, or 33.

8. The recombinant polypeptide of any one of claims 5-7, wherein the payload protein is a therapeutic peptide or protein.

9. A nucleic acid molecule encoding for the signal peptide of any one of claims 1-4.

10. A nucleic acid molecule encoding for the recombinant polypeptide of any one of claims 5-8.

11. A vector comprising the nucleic acid molecule of claim 9 or claim 10.

12. A cell comprising the nucleic acid molecule of claim 9 or claim 10 or the vector of claim 11.

13. A composition comprising the nucleic acid molecule of claim 9 or claim 10 or the vector of claim 11. ACTIVE / 131743364.1 188Attorney Docket No. UTSD 4319 (106546-823037)(SIGY-005WO) PATENT 14. A method for treating a disease or disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of the nucleic acid molecule of claim 10 to the subject, thereby treating the disease or disorder.

15. The method of claim 14, wherein the disease or disorder is cancer.

16. A method for treating cancer in a subject in need thereof, the method comprising administering to the subject a vector comprising a nucleic acid molecule encoding for a signal peptide fused or linked to a payload protein, wherein the signal peptide is the signal peptide of any one of claims 1-4 and wherein the payload protein is a therapeutic peptide or protein useful for the treatment of cancer. ACTIVE / 131743364.1 189

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