mRNA vaccine for peanut allergy treatment

Abstract

Disclosed herein are lipid nanoparticles comprising messenger RNA (mRNA) molecules encoding deepitoped Ara h 1 and / or de-epitoped Ara h 2, vaccines comprising the nanoparticles and methods for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.

Description

P-639811-PCMRNA VACCINE FOR PEANUT ALLERGY TREATMENTSEQUENCE LISTING

[0001] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on September 12, 2025, is named P-639811-PC_SL.xml and is 33,592 bytes in size.FIELD OF DISCLOSURE

[0002] The disclosure presented herein is in the field of messenger RNA (mRNA) vaccine, and particularly relates to lipid nanoparticles comprising mRNA molecules encoding deepitoped Ara h 1 and de-epitoped Ara h 2, vaccines comprising the lipid nanoparticles and methods for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.BACKGROUND

[0003] Peanut allergy is among the most common food allergies and is the most common cause of fatal food reactions and anaphylaxis (Lange et al., Allergo journal international 30 (2021): 261-269). The prevalence of peanut allergy has increased 3.5-fold over the past 2 decades, reaching 1.4% to 2% in Europe and the US (Lange et al., Allergo journal international 30 (2021): 261-269). Unlike other food allergies that tend to resolve in childhood or adolescence, peanut allergy persists into adulthood in approximately 75% to 80% of cases (reviewed in Lieberman, et al., Allergy 76.5 (2021): 1367-1384). Allergies to peanuts have a range of clinical presentations from mild cutaneous manifestations to severe anaphylaxis, a potentially life threatening systemic allergic reaction that usually occurs within minutes of exposure. The daily burden on patients with peanut allergy and their families can be substantial, resulting in a poorer quality of life due to the potential dangers in their environment and the fear of fatal anaphylaxis (Peters et al., Pediatric Allergy and Immunology 32.4 (2021): 647-657).P-639811-PC

[0004] The allergic reaction to peanut allergens is mediated through IgE antibodies. Allergens bound by IgE antibodies activate mast cells and basophils via the fragment crystallizable epsilon receptors (FceR) leading to their degranulation and release of histamines and cytokines into the blood which induces hypersensitivity reactions and anaphylaxis. Therapeutic approaches to peanut allergy mainly involve allergen immunotherapy whereby frequent administration of small and gradually increasing amounts of allergen first lead to desensitization of mast cells and basophils. This is followed by the induction of therapeutically beneficial allergen-specific IgG antibodies which inhibit IgE-mediated responses, and eventually a shift of allergen specific T and B cell responses away from a pathogenic phenotype (Durham and Shamji, Nature Reviews Immunology 23.5 (2023): 317-328).

[0005] There are two FDA-approved therapies for peanut allergy: Palforzia®, an oral allergen immunotherapy using whole peanut protein, and Xolair®, an injectable antibody that inhibits IgE antibody activation of FceR upon allergen exposure (Barshow et al., Annual Review of Immunology 42 (2024); Erlich, Deborah. American Family Physician 105.1 (2022): 20-21).

[0006] Known immunotherapies compositions have issues with safety and compliance and provide only short term protective effects.

[0007] In recent years, mRNA therapies have emerged as a promising avenue for various diseases, offering targeted and potentially safer alternatives. In contrast to DNA vaccines, mRNA vaccines cannot integrate into the host genome and are transiently expressed. Recent murine studies have demonstrated that mRNA vaccines have the potential to treat allergies through induction of a long-term memory response (Hattinger, et al., Journal of Immunology Research 2015.1 (2015): 797421) and by skewing the Th2 response towards tolerogenic phenotype (Xu, et al., ACS nano 17.5 (2023): 4942-4957).

[0008] In light of these auspicious results, there is still a need for mRNA vaccine compositions optimized for treating peanut allergy, e,g., mRNA vaccine compositions comprising a specific mRNA molecule encoding modified and safe proteins with specific UTR sequences and signal peptides that can overcome the disadvantages of existingP-639811-PC treatments and reduce the risk of hypersensitivity reactions while still inducing therapeutically beneficial allergen-specific immune responses. The choice of specific UTRs, signal peptides and other components of the mRNA molecule (such as PolyA length and specific capping) can greatly influence the stability and expression level of the mRNA molecules which in turn can enhance the immunotherapeutic potential of the mRNA vaccine.

[0009] Advantageously, such alternative compositions comprise mRNA molecules encoding modified variants (de-epitoped) of the two immunodominant peanut allergens, Ara h 1 and Ara h 2 (Palladino, Molecular immunology 100 (2018): 58-70.). Both modified allergens have substantially reduced IgE antibody binding but retain immunogenicity through allergen-specific IgG binding and activation of T cells, and can overcome the challenges of the current therapies by safely and quickly modulating immune responses to peanut allergens.SUMMARY

[0010] Disclosed herein is a mRNA molecule comprising at least one 5' untranslated region (5' UTR), at least one 3' untranslated region (3' UTR), and at least one an ORF encoding de-epitoped Ara h 1 or de-epitoped Ara h 2. In one aspect, the mRNA molecule comprises at least one 5' untranslated region (5' UTR), an ORF encoding de- epitoped Ara h 1, and at least one 3' untranslated region (3' UTR). In another aspect, the mRNA molecule comprises at least one 5' untranslated region (5' UTR), an ORF encoding de-epitoped Ara h 2, and at least one 3' untranslated region (3' UTR).

[0011] In another aspect, the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 15, or a fragment or variant thereof. In another aspect, the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 8, or a fragment or variant thereof. In another aspect, the 3' UTR comprises the nucleic acid sequence of SEQ ID NO: 9 or SEQ ID NO: 10. In another aspect, the mRNA molecule further comprises a sequence encoding at least one signal sequence. In another aspect, the signal sequence comprises a nucleic acid sequenceP-639811-PC encoding SEQ ID NO: 5. In another aspect, the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

[0012] In another aspect, the mRNA molecule comprises of the following structural elements: (i) 5' untranslated region (5' UTR) having the nucleic acid sequence of SEQ ID NO: 8; (ii) a signal sequence comprising the nucleic acid sequence of SEQ ID NO: 6; (iii) an ORF encoding de-epitoped Ara h 1 having the nucleic acid sequence of SEQ ID NO: 2; (iv) a 3' untranslated region (3' UTR) having the nucleic acid sequence of SEQ ID NO: 9 or SEQ ID NO: 10; and (v) a poly(A) tail.

[0013] In another aspect, the mRNA molecule comprises of the following structural elements: (i) 5' untranslated region (5' UTR) having the nucleic acid sequence of SEQ ID NO: 8; (ii) an ORF encoding de-epitoped Ara h 2 having the nucleic acid sequence of SEQ ID NO: 4 or SEQ ID NO: 16; (iii) a 3' untranslated region (3' UTR) having the nucleic acid sequence of SEQ ID NO: 9 or SEQ ID NO: 10; and (iv) a poly(A) tail.

[0014] In another aspect, disclosed herein is a mRNA molecule comprising a sequence selected from SEQ ID NOs: 17 and 19. In another aspect, disclosed herein is a mRNA molecule comprising a sequence selected from SEQ ID NOs: 18 and 20. In another aspect, disclosed herein is a mRNA molecule comprising a sequence having at least 90%, 95%, 97% or 99% similarity to sequence selected from the group consisting of SEQ ID NOs: 17, 18, 19 and 20.

[0015] In another aspect, the mRNA comprises one or more modified nucleotides. In another aspect, the modification is Nl- methylpseudouridine.

[0016] In another aspect, disclosed herein is a pharmaceutically acceptable composition comprising a de-epitoped Ara h 1 mRNA molecule described herein and a de-epitoped Ara h 2 mRNA molecule described herein. In some aspects, the de-epitoped Ara h 1 mRNA molecule and the de-epitoped Ara h 2 mRNA molecule are present in a ratio of about 10:0.1 to about 0.1:10 (w / w).

[0017] In another aspect, disclosed herein is a lipid nanoparticle (LNP) encapsulating the a) de-epitoped Ara h 1 mRNA selected from SEQ ID NO 17 or 19, and b) a de-epitoped Ara h 2 mRNA selected from SEQ ID NO 18 and 20. In some aspects, theP-639811-PC weight ratio of the de-epitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 in the lipid nanoparticle is about 1:1 (w:w). In some aspects, the lipid nanoparticle comprises [(4-hydroxybutyl)azanediyl]di(hexane-6,l-diyl) bis(2-hexyldecanoate), 1,2- distearoyl-sn-glycero-3-phosphocholine, cholesterol and(Methoxypolyethyleneglycoloxy(2000)-N,N-ditetradecylacetamide).

[0018] In another aspect, disclosed herein is a vaccine comprising the LNP described herein. According to some aspects, the vaccine is formulated for intramuscular injection.

[0019] In another aspect, disclosed herein is a pharmaceutical composition comprising the LNP described herein and a pharmaceutically acceptable excipient.

[0020] In another aspect, disclosed herein is a method for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, the method comprising administering to the subject the mRNA described herein, thereby inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.

[0021] In another aspect, disclosed herein is a method for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, the method comprising administering to the subject the vaccine or the pharmaceutical composition described herein, thereby inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.

[0022] According to some aspects, the administration is intramuscular, intravenous, subcutaneous, or intradermal administration. According to some aspects, the number of doses administered to the subject is at least 3. According to some aspects, the mRNA, composition or vaccine is administered every 1 to 24 weeks.

[0023] In another aspect, disclosed herein is a method of reducing a chronic risk of anaphylaxis in a patient suffering from a peanut allergy, comprising administering intramuscularly to the patient a 30 microgram or 100 microgram dose of a mRNAP-639811-PC encoding a modified peanut protein selected the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, or a mixture thereof, every 4 or 12 weeks.

[0024] In another aspect, disclosed herein is a method of reducing an allergic reaction to peanuts in a subject, the method comprising administering a 30 microgram or 100 microgram dose of a 1:1 (w:w) mixture of SEQ ID NO: 17 and SEQ ID NO. 18 wherein the method comprises reducing the severity of the peanut allergic reaction in the subject or reducing the incidence of allergic reaction in the subject to peanuts.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 schematically shows the timeline for the immunotherapeutic efficacy study of the selected candidate mRNA molecules using a peanut allergy mouse model.

[0026] Figure 2 schematically shows the timeline for the immunotherapeutic potential study. Naive female C3H / HeJ mice were administered 2 IM doses of 2 pg deepitoped (DE)-Ara h 1+DE-Ara h 2 mRNA (n=6 per group, respectively) on days 1 and 22. All groups were administered an additional IM dose (20 pg) on day 47. Sera samples were harvested for analysis of anti-DE-Ara h 1 and anti-DE-Ara h 2 IgG titers.

[0027] Figure 3A shows the anti-DE-Ara h 2 IgGl response following IM administration of different DE-Ara h 1+DE-Ara h 2 mRNA formulations to naive mice. Naive female C3H / HeJ mice (groups designated B-F, described in Table 2) were administered 2 IM doses of 2 pg (n=6) on days 1 and 22. All groups were then administered an additional IM dose (20 pg) on day 47. Anti-DE-Ara h 2 IgGl antibody titers were determined on days 29, 43 and 61 by ELISA.

[0028] Figure 3B shows the anti-DE-Ara h 2 lgG2a response following IM administration of different DE-Ara h 1+DE-Ara h 2 mRNA formulations to naive mice. Naive female C3H / HeJ mice (groups designated B-F, described in Table 2) were administered 2 IM doses of 2 pg (n=6) on days 1 and 22. All groups were then administered an additional IM dose (20 pg) on day 47. Anti-DE-Ara h 2 lgG2a antibody titers were determined on days 29, 43 and 61 by ELISA.P-639811-PC

[0029] Figure 3C shows the anti-DE-Ara h 1 IgGl response following IM administration of different DE-Ara h 1+DE-Ara h 2 mRNA formulations to naive mice. Naive female C3H / HeJ mice (groups designated B-F, described in Table 2) were administered 2 IM doses of 2 pg (n=6) on days 1 and 22. All groups were then administered an additional IM dose (20 pg) on day 47. Anti-DE-Ara h 1 IgGl antibody titers were determined on days 29 and 61 by ELISA.

[0030] Figure 3D shows the anti-DE-Ara h 1 lgG2a response following IM administration of different DE-Ara h 1+DE-Ara h 2 mRNA formulations to naive mice. Naive female C3H / HeJ mice (groups designated B-F, described in Table 2) were administered 2 IM doses of 2 pg (n=6) on days 1 and 22. All groups were then administered an additional IM dose (20 pg) on day 47. Anti-DE-Ara h 1 lgG2a antibody titers were determined on days 29 and 61 by ELISA.

[0031] Figure 3E shows the anti-DE-Ara h 1 and anti-DE-Ara h 2 IgGl responses following IM administration of different DE-Ara h 1+DE-Ara h 2 mRNA to naive mice. Naive female C3H / HeJ mice (groups designated A & E, described in Table 2) were administered 2 IM doses of 2 pg (n=6) on days 1 and 22. All groups were then administered an additional IM dose (20 pg) on day 47. Anti-DE-Ara h 1 (left) and Anti-DE-Ara h 2 IgGl (right) antibody titers were determined on days 29, (43 -only for DE-Ara h 2), 61, 82, 103, 124, 152, 180 and 208 by ELISA.

[0032] Figure 3F shows the anti-DE-Ara h 1 and anti-DE-Ara h 2 lgG2a responses following IM administration of different DE-Ara h 1+DE-Ara h 2 mRNA to naive mice. Naive female C3H / HeJ mice (groups designated A & E, described in Table 2) were administered 2 IM doses of 2 pg (n=6) on days 1 and 22. All groups were then administered an additional IM dose (20 pg) on day 47. Anti-DE-Ara h 1 and Anti-DE-Ara h 2 lgG2a antibody titers were determined on days 29, (43 -only for DE-Ara h 2), 61, 82, 103, 124, 152, 180 and 208 by ELISA.DETAILED DESCRIPTIONP-639811-PC

[0033] In the following detailed description, numerous specific details and embodiments are set forth in order to provide a thorough understanding of the lipid nanoparticles disclosed herein and their uses. In some instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present disclosure. mRNA molecules

[0034] In some embodiments, the present disclosure relates to a messenger RNA (mRNA) molecule comprising an open reading frame (ORF) encoding de-epitoped (DE) Ara h 1. In some embodiments, the present disclosure relates to a messenger RNA (mRNA) molecule comprising an open reading frame (ORF) encoding de-epitoped (DE) Ara h 2. In some embodiments, the present disclosure relates to a messenger RNA (mRNA) molecule comprising an open reading frame (ORF) encoding de-epitoped Ara h 1 and an open reading frame (ORF) encoding de-epitoped Ara h 2.

[0035] The terms "polynucleotide" or "nucleotide sequence" may encompasses a single or double stranded nucleic acid sequence in the form of an RNA sequence, such as messenger RNA (mRNA), a complementary polynucleotide sequence (cDNA), a genomic polynucleotide sequence and / or a composite polynucleotide sequence (e.g., a combination of the above). A polynucleotide may be linear or branched, and optionally contains synthetic, non-natural or altered nucleotide bases.

[0036] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleotide sequence set forth in SEQ ID NO: 2, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleotide sequence set forth in SEQ ID NO: 2, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 2.P-639811-PC

[0037] Fragment with reference to a mRNA, relates to a part of that sequence, e.g.,- a sequence which represents the nucleic acid sequence shortened at the 5'- and / or 3'-end(s). A fragment of a nucleic acid sequence may include at least 80%, or at least 90%, 95%, 96%, 97%, 98%, or 99% of the nucleotide residues from the nucleic acid sequence. Contemplated fragments of RNA molecules may retain RNA stability and / or translational efficiency.

[0038] Nucleic acid variants contemplated herein include single or multiple nucleotide deletions, additions, mutations, substitutions and / or insertions in comparison with the reference nucleic acid. Deletions include removal of one or more nucleotides from the reference nucleic acid. Addition variants comprise 5'- and / or 3'-terminal fusions of one or more nucleotides, such as 1, 2, 3, 5, 10, 20, 30, 50, or more nucleotides. In the case of substitutions, at least one nucleotide in the sequence is removed and at least one other nucleotide is inserted in its place (such as transversions and transitions). Mutations include a basic sites, crosslinked sites, and chemically altered or modified bases. Insertions include the addition of at least one nucleotide into the reference nucleic acid.

[0039] Variants of specific nucleic acid sequences may have at least one functional property of a specific sequence and can be functionally equivalent to a specific sequence, e.g., nucleic acid sequences exhibiting properties identical or similar to those of the specific nucleic acid sequences. These homologous sequences are variants of other nucleic acid sequences.

[0040] Preferably the degree of identity between a given nucleic acid sequence and a nucleic acid sequence which is a variant of said given nucleic acid sequence is at least 80%, at least 85%, at least 90% or at least 95%, 96%, 97%, 98% or 99%. The degree of identity may be given for a region of at least about 30, at least about 50, at least about 70, at least about 90, at least about 100, at least about 150, at least about 200, at least about 250, at least about 300, or at least about 400 nucleotides. For example, the degree of identity can be given for the entire length of the reference nucleic or amino acid sequence.P-639811-PC

[0041] The term "% identical" is intended to refer, in particular, to a percentage of nucleotides or amino acids which are identical in an optimal alignment between two sequences to be compared, with said percentage being purely statistical, and the differences between the two sequences may be randomly distributed over the entire length of the sequence and the sequence to be compared may comprise additions or deletions in comparison with the reference sequence, in order to obtain optimal alignment between two sequences. Comparisons of two sequences are usually carried out by comparing said sequences, after optimal alignment, with respect to a segment or "window of comparison", in order to identify local regions of corresponding sequences. The optimal alignment for a comparison may be carried out manually or with the aid of the local homology algorithm by Smith and Waterman, 1981, Ads App. Math. 2:482, with the aid of the local homology algorithm by Needleman and Wunsch, 1970, J. Mol.

[0042] Methods for the determination of sequence identity are known in the field and include, without limitation, the Basic Local Alignment Search Tool (BLAST).

[0043] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 4, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 4, or a sequence having at least 85%, preferably at least 90%, more preferably, at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 4.

[0044] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 16, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 16, or a sequence having at least 85%, preferably at least 90%, more preferably, at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encodingP-639811-PC de-epitoped Ara h 2 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 16.

[0045] In some embodiments, de-epitoped Ara h 1 comprises an amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the de-epitoped Ara h 1 comprises the amino acid sequence set forth in SEQ ID NO: 1, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 1. In some embodiments, the de-epitoped Ara h 1 comprises an amino acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 1.

[0046] In some embodiments, de-epitoped Ara h 2 comprises an amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the de-epitoped Ara h 2 comprises the amino acid sequence set forth in SEQ ID NO: 3, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 3. In some embodiments, the de-epitoped Ara h 2 comprises an amino acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 3.

[0047] In some embodiments, de-epitoped Ara h 2 comprises an amino acid sequence set forth in SEQ ID NO: 21. In some embodiments, the de-epitoped Ara h 2 comprises the amino acid sequence set forth in SEQ ID NO: 21, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 21. In some embodiments, the de-epitoped Ara h 2 comprises an amino acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 21.

[0048] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises a nucleic acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95%P-639811-PC identical to SEQ ID NO: 18 or 20. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleic acid sequence set forth in SEQ ID NO: 18, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 2 comprises the nucleic acid sequence set forth in SEQ ID NO: 20, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 20.

[0049] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises a nucleic acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 17 or SEQ ID NO: 19. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleic acid sequence set forth in SEQ ID NO: 17, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 17. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleic acid sequence set forth in SEQ ID NO: 19, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 19.

[0050] In some embodiments, disclosed herein is a mRNA molecule comprising: (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 1 comprising the nucleic acid sequence of SEQ ID NO: 2 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0051] In some embodiments of the mRNA molecule, the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 8.

[0052] In some embodiments of the mRNA molecule, the mRNA molecule further comprises a sequence segment encoding at least one signal sequence.

[0053] In some embodiments of the mRNA molecule, the signal sequence comprises a nucleic acid sequence encoding SEQ ID NO: 5. In some embodiments of theP-639811-PC mRNA molecule, the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

[0054] In some embodiments the mRNA molecule comprises the elements: (i) 5' untranslated region (5' UTR) comprising the nucleic acid sequence of SEQ ID NO: 15; (ii) a signal sequence comprising the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7; (iii) an ORF encoding de-epitoped Ara h 1 having the nucleic acid sequence of SEQ ID NO: 2; (iv) a 3' untranslated region (3' UTR) having the nucleic acid sequence of SEQ ID NO: 9 or SEQ ID NO: 10; and (v) a poly(A) tail.

[0055] In some embodiments the mRNA molecule comprises (i) 5' untranslated region (5' UTR) having the nucleic acid sequence of SEQ ID NO: 8; (ii) a signal sequence comprising the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7; (iii) an ORF encoding de-epitoped Ara h 1 having the nucleic acid sequence of SEQ ID NO: 2; (iv) a 3' untranslated region (3' UTR) having the nucleic acid sequence of SEQ ID NO: 10; and (v) a poly(A) tail.

[0056] In some embodiments, disclosed herein is a mRNA molecule comprising: (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 1 comprising the amino acid sequence of SEQ ID NO: 1 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0057] In some embodiments the mRNA molecule comprises (i) 5' untranslated region (5' UTR) having the nucleic acid sequence of SEQ ID NO: 8; (ii) a signal sequence comprising the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7; (iii) an ORF encoding de-epitoped Ara h 1 having the amino acid sequence of SEQ ID NO: 1; (iv) a 3' untranslated region (3' UTR) having the nucleic acid sequence of SEQ ID NO: 10; and (v) a poly(A) tail.

[0058] In some embodiments, disclosed herein is a mRNA molecule comprising: (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 2 comprising the nucleic acid sequence of SEQ ID NO: 4P-639811-PC or SEQ ID NO: 16 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0059] In some embodiments the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding deepitoped Ara h 2 comprising the nucleic acid sequence of SEQ ID NO: 4, or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0060] In some embodiments the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding deepitoped Ara h 2 comprising the nucleic acid sequence of SEQ ID NO: 16, or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0061] In some embodiments the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 8 or a fragment or variant thereof; (ii) an ORF encoding deepitoped Ara h 2 comprising the nucleic acid sequence of SEQ ID NO: 4, or a fragment or variant thereof; (iii) at least one 3' UTR comprising SEQ ID NO: 10, or a fragment or variant thereof; and (iv) a poly(A) tail.

[0062] In some embodiments the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 8 or a fragment or variant thereof; (ii) an ORF encoding deepitoped Ara h 2 comprising the nucleic acid sequence of SEQ ID NO: 16, or a fragment or variant thereof; (iii) at least one 3' UTR comprising SEQ ID NO: 10, or a fragment or variant thereof; and (iv) a poly(A) tail.

[0063] In some embodiments, disclosed herein is a mRNA molecule comprising (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 3 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0064] In some embodiments, disclosed herein is a mRNA molecule comprising (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORFP-639811-PC encoding de-epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 21, or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0065] In some embodiments, disclosed herein is a mRNA molecule comprising (i) at least one 5' UTR comprising SEQ ID NO: 8 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 3 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0066] In some embodiments, disclosed herein is a mRNA molecule comprising (i) at least one 5' UTR comprising SEQ ID NO: 8 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 21, or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

[0067] In some embodiments the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 8 or a fragment or variant thereof; (ii) an ORF encoding de- epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 3, or a fragment or variant thereof; (iii) at least one 3' UTR comprising SEQ ID NO: 10, or a fragment or variant thereof; and (iv) a poly(A) tail.

[0068] In some embodiments the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 8 or a fragment or variant thereof; (ii) an ORF encoding de- epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 21, or a fragment or variant thereof; (iii) at least one 3' UTR comprising SEQ ID NO: 10, or a fragment or variant thereof; and (iv) a poly(A) tail.

[0069] In some embodiments the mRNA molecule comprises a sequence selected from SEQ ID NO: 17 and SEQ ID NO: 19.

[0070] In some embodiments the mRNA molecule comprises a sequence selected from SEQ ID NOs: 18 and SEQ ID NO: 20.P-639811-PC

[0071] In some embodiments the mRNA molecule comprises a sequence having at least 90%, 95%, 97% or 99% similarity to sequence selected from the group consisting of SEQ ID NOs: 17, 18, 19 and 20.

[0072] In some embodiments, the encoded or translated de-epitoped Ara h 1 and the encoded or translated de-epitoped Ara h 2 comprise recombinant Ara h 1 and Ara h 2 variant sequences described in detail in International PCT Publication WO 2023 / 012652, published on February 9, 2023, incorporated herein by reference.Modified RNAs

[0073] In some embodiments, the mRNA molecules may be unmodified (i.e., containing only natural ribonucleotides A, U, C, and / or G linked by phosphodiester bonds), or chemically modified (e.g., including nucleotide analogs such as pseudouridines (e.g., N 1 methyl pseudouridine), 2' -fluoro ribonucleotides, and 2'-methoxy ribonucleotides, and / or phosphorothioate bonds).

[0074] In some embodiments, the present disclosure provides compositions comprising modified RNAs and methods of use thereof. In some embodiments, the modified RNA comprises one or more modified nucleoside residues. For example, in some embodiments, an RNA comprising a nucleotide sequence at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to a sequence listed in Table 1, comprises one or more modified nucleoside residues.

[0075] In some embodiments, an RNA as described herein refers to a messenger RNA.

[0076] In some embodiments, all uridine residues are modified as described herein. In some embodiments, one or more of the RNAs as described herein are nucleoside modified RNAs. In other embodiments, two or more of the RNAs as described herein are nucleoside modified RNAs. In other embodiments, three or more of the RNAs as described herein are nucleoside modified RNAs.P-639811-PC

[0077] In some embodiments, the modified nucleoside of the methods and compositions of the present disclosure is m5C (5-methylcytidine). In another embodiment, the modified nucleoside is m5U (5-methyluridine). In another embodiment, the modified nucleoside is m6A (N6-methyladenosine). In another embodiment, the modified nucleoside is s2U (2-thiouridine). In another embodiment, the modified nucleoside is QJ (pseudouridine). In another embodiment, the modified nucleoside is Um (2'-O-methyluridine).

[0078] In some embodiments, a modified nucleoside is m:A (1-methyladenosine), m2A (2-methyladenosine), m5A (N6-methyladenosine), Am (2'-O-methyladenosine), ms2m5A (2-methylthio-N6-methyladenosine), i5A (N6-isopentenyladenosine), ms2i5A (2- methylthio-N6-isopentenyladenosine), io5A (N6-(cis-hydroxyisopentenyl)adenosine), ms2io5A (2-methylthio-N6-(cis-hydroxyisopentenyl) adenosine), g5A (N6- glycinylcarbamoyladenosine), t5A (N6-threonylcarbamoyladenosine), ms2t5A (2- methylthio-N6-threonyl carbamoyladenosine), m5t5A (N6-methyl-N6- threonylcarbamoyladenosine), hn5A (N6-hydroxynorvalylcarbamoyladenosine), ms2hn5A (2-methylthio-N6-hydroxynorvalyl carbamoyladenosine), Ar(p) (2'-O-ribosyladenosine (phosphate)), I (inosine), m1! (1-methylinosine), rr m (l,2'-O-dimethylinosine), m3C (3- methylcytidine), m5C (5-methylcytidine), Cm (2'-O-methylcytidine), s2C (2-thiocytidine), ac4C (N4-acetylcytidine), f5C (5-formylcytidine), m5Cm (5,2'-O-dimethylcytidine), ac4Cm (N4-acetyl-2'-O-methylcytidine), k2C (lysidine), m4G (1-methylguanosine), m2G (N2- methylguanosine), m7G (7-methylguanosine), Gm (2'-O-methylguanosine), m22G (N2,N2- dimethylguanosine), m2Gm (N2,2'-O-dimethylguanosine), m22Gm (N2,N2,2'-O- trimethylguanosine), Gr(p) (2'-O-ribosylguanosine (phosphate)), yW (wybutosine), 02yW (peroxywybutosine), OHyW (hydroxywybutosine), OHyW* (undermodified hydroxywybutosine), imG (wyosine), mimG (methylwyosine), Q (queuosine), oQ (epoxyqueuosine), galQ (galactosyl-queuosine), manQ (mannosyl-queuosine), preQO (7- cyano-7-deazaguanosine), preQi (7-aminomethyl-7-deazaguanosine), G+(archaeosine), Y (pseudouridine), D (dihydrouridine), m5U (5-methyluridine), Um (2'-O-methyluridine), m5Um (5,2'-O-dimethyluridine), nr^Y (1-methylpseudouridine), Ym (2'-O-P-639811-PC methylpseudouridine), s2U (2-thiouridine), s4U (4-thiouridine), m5s2U (5-methyl-2- thiouridine), s2Um (2-thio-2'-O-methyluridine), acp3U (3-(3-amino-3- carboxypropyl)uridine), ho5U (5-hydroxyuridine), mo5U (5-methoxyuridine), cmo5U (uridine 5-oxyacetic acid), mcmo5U (uridine 5-oxyacetic acid methyl ester), chm5U (5- (carboxyhydroxymethyl)uridine), mchm5U (5-(carboxyhydroxymethyl)uridine methyl ester), mcm5U (5-methoxycarbonylmethyluridine), mcm5Um (5- methoxycarbonyl methyl-2'-0-methyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2- thiouridine), nm5s2U (5-aminomethyl-2-thiouridine), mnm5U (5- methylaminomethyluridine), mnm5s2U (5-methylaminomethyl-2-thiouridine), mnm5se2U (5-methylaminomethyl-2-selenouridine), ncm5U (5-carbamoylmethyluridine), ncm5Um (5-carbamoylmethyl-2'-O-methyluridine), cmnm5U (5- carboxymethylaminomethyluridine), cmnm5Um (5-carboxymethylaminomethyl- 2'-O- methyluridine), cmnm5s2U (5-carboxymethylaminomethyl-2-thiouridine), m52A (N6,N6- dimethyladenosine), Im (2'-O-methylinosine), m4C (N4-methylcytidine), m4Cm (N4,2'-O- dimethylcytidine), hm5C (5-hydroxymethylcytidine), m3U (3-methyluridine), m1acp3Y (1- methyl-3-(3-amino-3-carboxypropyl) pseudouridine), cm5U (5-carboxymethyluridine), m5Am (N6,2'-O-dimethyladenosine), m52Am (N6,N6,2'-O-trimethyladenosine), m2-7G (N2,7-dimethylguanosine), m2-2'7G (N2,N2,7-trimethylguanosine), m3Um (3,2'-O- dimethyluridine), m5D (5-methyldihydrouridine), m3Y (3-methylpseudouridine), f5Cm (5- formyl-2'-O-methylcytidine), rr^Gm (l,2'-O-dimethylguanosine), m:Am (l,2'-O- dimethyladenosine), tm5U (5-taurinomethyluridine), tm5s2U (5-taurinomethyl-2- thiouridine), imG-14 (4-demethylwyosine), imG2 (isowyosine), ac5A (N6- acetyladenosine), inm5U (5-(isopentenylaminomethyl)uridine), inm5s2U (5- (isopentenylaminomethyl)- 2-thiouridine), inm5Um (5-(isopentenylaminomethyl)- 2'-O- methyluridine), m2-7Gm (N2,7,2'-O-trimethylguanosine), m42Cm (N4,N4,2'-O- trimethylcytidine), C+(agmatidine), m8A (8-methyladenosine), gmnm5s2U (geranylated 5- methylaminomethyl-2-thiouridine), gcmnm5s2U (geranylated 5- carboxymethylaminomethyl-2-thiouridine), or cnm5U (5-cyanomethyl-uridine).P-639811-PC

[0079] In some embodiments, modified nucleoside residues are pseudouridine or pseudouridine family residues.

[0080] In some embodiments, the modified mRNA comprises pseudouridine residues. In some embodiments, pseudouridine refers to the C-glycoside isomer of the nucleoside uridine. In some embodiments, pseudouridine residues comprise rr^acp3^ (1- methyl-3-(3-amino-5-carboxypropyl)pseudouridine, m1^ (1-methylpseudouridine), QJm (2'-O-methylpseudouridine, m5D (5-methyldihydrouridine), m3|JJ (3- methylpseudouridine), or a combination thereof. In some embodiments, said pseudouridine residues comprise 1-methylpseudouridine residues instead of uridine.

[0081] In some embodiments, modified nucleoside residues are pseudouridine analogues. In some embodiments, a "pseudouridine analog" is any modification, variant, isoform or derivative of pseudouridine. For example, pseudouridine analogs include but are not limited to 1-carboxymethyl-pseudouridine, 1-propynyl-pseudouridine, 1- taurinomethyl-pseudouridine, l-taurinomethyl-4-thio-pseudouridine, 1- methylpseudouridine (rr^Y), l-methyl-4-thio-pseudouridine (m1s4Y), 4-thio-l-methyl- pseudouridine, 3-methyl-pseudouridine (m3Y), 2-thio-l-methyl-pseudouridine, 1- methyl-l-deaza-pseudouridine, 2-thio-l-methyl-l-deaza-pseudouridine, dihydropseudouridine, 2-thio-dihydropseudouridine, 2-methoxyuridine, 2-methoxy-4- thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, Nl-methyl- pseudouridine, l-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp3Y), and 2'-O- methyl-pseudouridine (Ym).

[0082] In some embodiments, a modified nucleobase is a modified uracil. Exemplary nucleobases and nucleosides having a modified uracil include pseudouridine (Y), pyridin-4-one ribonucleoside, 5-aza-uridine, 6-aza-uridine, 2-thio-5-aza-uridine, 2- thio-uridine (s2U), 4-thio-uridine (s4U), 4-thio-pseudouridine, 2-thio-pseudouridine, 5- hydroxy-uridine (ho5U), 5-aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridine or 5- bromo-uridine), 3-methyl-uridine (m3U), 5-methoxy-uridine (mo5U), uridine 5-oxyacetic acid (cmo5U), uridine 5-oxyacetic acid methyl ester (mcmo5U), 5-carboxymethyl-uridine (cm5U), 1-carboxymethyl-pseudouridine, 5-carboxyhydroxymethyl-uridine (chm5U), 5-P-639811-PC carboxyhydroxymethyl-uridine methyl ester (mchm5U), 5-methoxycarbonylmethyl- uridine (mcm5U), 5-methoxycarbonylrnethyl-2-thio-uridine (mcm5s2U), 5-aminomethyl- 2-thio-uridine (nm5s2U), 5-methylaminomethyl-uridine (mnm5U), 5-methylaminomethyl- 2-thio-uridine (mnm5s2U), 5-methylaminornethyl-2-seleno-uridine (mnm5se2U), 5- carbamoylrnethyl-uridine (ncm5U), 5-carboxymethylaminornethyl-uridine (cmnm5U), 5- carboxymethylaminomethyl-2-thio-uridine (cmnm5s2U), 5-propynyl-uridine, 1-propynyl- pseudouridine, 5-taurinomethyl-uridine (tcm5U), 1-taurinomethyl-pseudouridine, 5- taurinomethyl-2-thio-uridine (trm5s2U), l-taurinomethyl-4-thio-pseudouridine, 5- methyl-uridine (m5U, i.e., having the nucleobase deoxythymine), 1-methylpseudouridine (rr^Y), 5-methyl-2-thio-uridine (m5s2U), l-methyl-4-thio-pseudouridine (m1s4Y), 4-thio-l- methyl-pseudouridine, 3-methyl-pseudouridine (m3Y), 2-thio-l-methyl-pseudouridine, 1-methyl-l-deaza-pseudouridine, 2-thio-l-methyl-l-deaza-pseudouridine, dihydrouridine (D), dihydropseudouridine, 5,6-dihydrouridine, 5-methyl-dihydrouridine (m5D), 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxy-uridine, 2- methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, Nl-methyl-pseudouridine (also known as 1-methylpseudouridine (rr^Y), 3-(3-amino-3- carboxypropyl)uridine (acp3U), l-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp3Y), 5-(isopentenylaminomethyl)uridine (inm5U), 5-(isopentenylaminomethyl)-2- thio-uridine (inm5s2U), a-thio-uridine, 2'-O-methyl-uridine (Um), 5,2'-O-dimethyl-uridine (m5Um), 2'-O-methyl-pseudouridine (Ym), 2-thio-2'-O-methyl-uridine (s2Um), 5- methoxycarbonylmethyl-2'-O-methyl-uridine (mcm5Um), 5-carbamoylmethyl-2'-|3- methyl-uridine (ncm5Um), 5-carboxymethylaminomethyl-2'-O-methyl-uridine (cmnm5Um), 3,2'-O-dimethyl-uridine (m3Um), 5-(isopentenylaminomethyl)-2'-|3-methyl- uridine (inm5Um), 1-thio-uridine, deoxythymidine, 2'-F-ara-uridine, 2'-F-uridine, 2'-OH- ara-uridine, 5-(2-carbomethoxyvinyl)uridine, and 5-[3-(l-E-propenylamino)uridine.

[0083] In some embodiments, a modified nucleobase is a modified cytosine. Exemplary nucleobases and nucleosides having a modified cytosine include 5-aza- cytidine, 6-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine (m3C), N4-acetyl-cytidine (ac4C), 5-formyl-cytidine (f5C), N4-methyl-cytidine (m4C), 5-methyl-cytidine (m5C), 5-halo-P-639811-PC cytidine (e.g., 5-iodo-cytidine), 5-hydroxymethyl-cytidine (hm5C), 1-methyl- pseudoisocytidine, pyrrolo-cytidine, pyrrolo-pseudoisocytidine, 2-thio-cytidine (s2C), 2- thio-5-methyl-cytidine, 4-thio-pseudoisocytidine, 4-thio-l-methyl-pseudoisocytidine, 4- thio-l-methyl-l-deaza-pseudoisocytidine, 1-methyl-l-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine, 5-methyl-zebularine, 5-aza-2-thio-zebularine, 2-thio- zebularine, 2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine, 4-methoxy- pseudoisocytidine, 4-methoxy-l-methyl-pseudoisocytidine, lysidine (I C), a-thio- cytidine, 2'-O-methyl-cytidine (Cm), 5,2'-O-dimethyl-cytidine (m5Cm), N4-acetyl-2'-O- methyl-cytidine (ac4Cm), N4,2'-O-dimethyl-cytidine (m4Cm), 5-formyl-2'-O-methyl- cytidine (f5Cm), N4,N4,2'-O-trimethyl-cytidine (m42Cm), 1-thio-cytidine, 2'-F-ara-cytidine, 2'-F-cytidine, and 2'-OH-ara-cytidine.

[0084] In some embodiments, a modified nucleobase is a modified adenine. Exemplary nucleobases and nucleosides having a modified adenine include 2-amino- purine, 2,6-diaminopurine, 2-amino-6-halo-purine (e.g., 2-amino-6-chloro-purine), 6- halo-purine (e.g., 6-chloro-purine), 2-amino-6-methyl-purine, 8-azido-adenosine, 7- deaza-adenine, 7-deaza-8-aza-adenine, 7-deaza-2-amino-purine, 7-deaza-8-aza-2- amino-purine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1-methyl- adenosine (rr^A), 2-methyl-adenine (m2A), N6-methyl-adenosine (m5A), 2-methylthio- N6-methyl-adenosine (ms2m5A), N6-isopentenyl-adenosine (i5A), 2-methylthio-N6- isopentenyl-adenosine (ms2i5A), N6-(cis-hydroxyisopentenyl)adenosine (io5A), 2- methylthio-N6-(cis-hydroxyisopentenyl)adenosine (ms2io5A), N6-glycinylcarbamoyl- adenosine (g5A), N6-threonylcarbamoyl-adenosine (t6A), N6-methyl-N6- threonylcarbamoyl-adenosine (m5t5A), 2-methylthio-N6-threonylcarbamoyl-adenosine (ms2g5A), N6,N6-dimethyl-adenosine (m52A), N6-hydroxynorvalylcarbamoyl-adenosine (hn5A), 2-methylthio-N6-hydroxynorvalylcarbamoyl-adenosine (ms2hn5A), N6-acetyl- adenosine (ac5A), 7-methyl-adenine, 2-methylthio-adenine, 2-methoxy-adenine, a-thio- adenosine, 2'-O-methyl-adenosine (Am), N6,2'-O-dimethyl-adenosine (m5Am), N6,N6,2'- O-trimethyl-adenosine (m52Am), l,2'-O-dimethyl-adenosine (rr^Am), 2'-|3- ribosyladenosine (phosphate) (Ar(p)), 2-amino-N6-methyl-purine, 1-thio-adenosine, 8-P-639811-PC azido-adenosine, 2'-F-ara-adenosine, 2'-F-adenosine, 2'-OH-ara-adenosine, and N6-(19- amino-pentaoxanonadecyl)-adenosine.

[0085] In some embodiments, a modified nucleobase is a modified guanine. Exemplary nucleobases and nucleosides having a modified guanine include inosine (I), 1- methyl-inosine (m1!), wyosine (imG), methylwyosine (mimG), 4-demethyl-wyosine (imG- 14), isowyosine (imG2), wybutosine (yW), peroxywybutosine (ozyW), hydroxywybutosine (OHyW), undermodified hydroxywybutosine (OHyW*), 7-deaza-guanosine, queuosine (Q), epoxyqueuosine (oQ), galactosyl-queuosine (galQ), mannosyl-queuosine (manQ), 7- cyano-7-deaza-guanosine (preQo), 7-aminomethyl-7 -deaza-guanosine (preQi), archaeosine (G+), 7-deaza-8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine,6-thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine (m7G), 6-thio-7-methyl-guanosine,7-methyl-inosine, 6-methoxy-guanosine, 1-methyl-guanosine (rr^G), N2-methyl- guanosine (m2G), N2,N2-dimethyl-guanosine (m22G), N2,7-dimethyl-guanosine (m2,7G), N2,N2,7-dimethyl-guanosine (m2,2,7G), 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1- methyl-6-thio-gua nosine, N2-methyl-6-th io-guanosine, N2,N2-dimethyl-6-thio- guanosine, a-thio-guanosine, 2'-O-methyl-guanosine (Gm), N2-methyl-2'-O-methyl- guanosine (m2Gm), N2,N2-dimethyl-2'-O-methyl-guanosine (m22Gm), l-methyl-2'-O- methyl-guanosine (rr^Gm), N2,7-dimethyl-2'-O-methyl-guanosine (m2 7Gm), 2'-O- methyl-inosine (Im), l,2'-O-dimethyl-inosine (m^m), and 2'-O-ribosylguanosine (phosphate) (Gr(p)).

[0086] The nucleobase of the nucleotide can be independently selected from a purine, a pyrimidine, a purine or pyrimidine analog. For example, the nucleobase can each be independently selected from adenine, cytosine, guanine, uracil, or hypoxanthine. In another embodiment, the nucleobase can also include, for example, naturally-occurring and synthetic derivatives of a base, including pyrazolo[3,4-d]pyrimidines, 5- methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, 2- aminoadenine, 6-methyl and other alkyl derivatives of adenine and guanine, 2-propyl and other alkyl derivatives of adenine and guanine, 2-thioura cil, 2-thiothymine and 2- thiocytosine, 5-propynyl uracil and cytosine, 6-azo uracil, cytosine and thymine, 5-uracilP-639811-PC(pseudouracil), 4-thiouracil, 8-halo (e.g., 8-bromo), 8-amino, 8-thiol, 8-thioalkyl, 8- hydroxyl and other 8-substituted adenines and guanines, 5-halo particularly 5-bromo, 5- trifluoromethyl and other 5-substituted uracils and cytosines, 7-methylguanine and 7- methyladenine, 8-azaguanine and 8-azaadenine, deazaguanine, 7-deazaguanine, 3- deazaguanine, deazaadenine, 7-deazaadenine, 3-deazaadenine, pyrazolo[3,4- d]pyrimidine, imidazo[l,5-a]l,3,5 triazinones, 9-deazapurines, imidazo[4,5-d] pyrazines, thiazolo[4,5-d]pyrimidines, pyrazin-2-ones, 1,2,4-triazine, pyridazine; and 1,3,5 triazine. When the nucleotides are depicted using the shorthand A, G, C, T or U, each letter refers to the representative base and / or derivatives thereof, e.g., A includes adenine or adenine analogs, e.g., 7-deaza adenine).

[0087] The modified nucleotides, which may be incorporated into a polynucleotide, primary construct, or RNA molecule, can be modified on the internucleoside linkage (e.g., phosphate backbone). Herein, in the context of the polynucleotide backbone, the phrases "phosphate" and "phosphodiester" are used interchangeably. Backbone phosphate groups can be modified by replacing one or more of the oxygen atoms with a different substituent. Further, the modified nucleosides and nucleotides can include the wholesale replacement of an unmodified phosphate moiety with another internucleoside linkage as described herein. Examples of modified phosphate groups include, but are not limited to, phosphorothioate, phosphoroselenates, boranophosphates, boranophosphate esters, hydrogen phosphonates, phosphoramidates, phosphorodiamidates, alkyl or aryl phosphonates, and phosphotriesters. Phosphorodithioates have both non-linking oxygens replaced by sulfur. The phosphate linker can also be modified by the replacement of a linking oxygen with nitrogen (bridged phosphoramidates), sulfur (bridged phosphorothioates), and carbon (bridged methylene-phosphonates).

[0088] The a-thio substituted phosphate moiety is provided to confer stability to RNA and DNA polymers through the unnatural phosphorothioate backbone linkages. Phosphorothioate DNA and RNA have increased nuclease resistance and subsequently a longer half-life in a cellular environment. Phosphorothioate linked polynucleotides,P-639811-PC primary constructs, or modified RNA molecules are expected to also reduce the innate immune response through weaker binding / activation of cellular innate immune molecules.

[0089] In some embodiments, a modified nucleoside includes an alpha-thio- nucleoside (e.g., 5'-O-(l-thiophosphate)-adenosine, 5'-O-(l-thiophosphate)-cytidine (a- thio-cytidine), 5'-O-(l-thiophosphate)-guanosine, 5'-O-(l-thiophosphate)-uridine, or 5'- O-(l-thiophosphate)-pseudouridine).

[0090] Other internucleoside linkages that may be employed according to the present disclosure, including internucleoside linkages which do not contain a phosphorous atom, are described herein below.

[0091] The polynucleotides, primary constructs, and modified RNA of the disclosure can include a combination of modifications to the sugar, the nucleobase, and / or the internucleoside linkage. In another embodiment, the purified preparation of RNA, oligoribonucleotide, or polyribonucleotide of the methods and compositions of the present disclosure comprises a combination of two or more of the above-described modifications. In another embodiment, the purified preparation of the RNA or oligoribonucleotide comprises a combination of three or more of the above-described modifications. In another embodiment, the purified preparation of the RNA or oligoribonucleotide comprises a combination of more than three of the above-described modifications.

[0092] In some embodiments, the modified RNAs comprise in vitro-synthesized modified RNAs.

[0093] In another embodiment, the nucleoside that is modified in an RNA, oligoribonucleotide, or polyribonucleotide of the methods and compositions of the present disclosure is uridine (U). In another embodiment, the modified nucleoside is cytidine (C). In another embodiment, the modified nucleoside is adenine (A). In another embodiment the modified nucleoside is guanine (G).

[0094] In another embodiment, the RNA of the methods and compositions of the present disclosure further comprises a poly-A tail. In another embodiment, the RNA ofP-639811-PC the methods and compositions of the present disclosure does not comprise a poly-A tail. Each possibility represents a separate embodiment of the present disclosure.

[0095] In another embodiment, the RNA of the methods and compositions of the present disclosure comprises an m7GpppG cap. In another embodiment, the RNA of the methods and compositions of the present disclosure does not comprise an m7GpppG cap. In another embodiment, the RNA of the methods and compositions of the present disclosure comprises a 3'-O-methyl-m7GpppG. In another embodiment, the RNA of methods and composition of the present disclosure comprise a non-reversible cap analog, which, in some embodiments, is added during transcription of the RNA. In another embodiment, the RNA of methods and composition of the present disclosure comprise an anti-reverse cap analog. Each possibility represents a separate embodiment of the present disclosure.

[0096] In another embodiment, the RNA of the methods and compositions of the present disclosure further comprises a cap-independent translational enhancer. In another embodiment, the RNA of the methods and compositions of the present disclosure does not comprise a cap-independent translational enhancer. In another embodiment, the cap-independent translational enhancer is a tobacco etch virus (TEV) cap-independent translational enhancer. In another embodiment, the cap-independent translational enhancer is any other cap-independent translational enhancer known in the art. Each possibility represents a separate embodiment of the present disclosure.

[0097] In some embodiments, "pseudouridine" refers to rr^acp3^ (l-methyl-3-(3- amino-5-carboxypropyl)pseudouridine. In another embodiment, the term refers to m1^ (1-methylpseudouridine). In another embodiment, the term refers to QJm (2'-O- methylpseudouridine. In another embodiment, the term refers to m5D (5- methyldihydrouridine). In another embodiment, the term refers to m3|JJ (3- methylpseudouridine). In another embodiment, the modified nucleoside is 4' (pseudouridine). In another embodiment, the term refers to a pseudouridine moiety that is not further modified. In another embodiment, the term refers to a monophosphate, diphosphate, or triphosphate of any of the above pseudouridines. In anotherP-639811-PC embodiment, the term refers to any other pseudouridine known in the art. Each possibility represents a separate embodiment of the present disclosure.

[0098] In another embodiment, a modified RNA comprises a modified nucleoside, which in some embodiments, comprises m5C, m5U, m5A, s2U, Y, 2'-O-methyl-U, 2'-O- methyl pseudouridine, or a combination thereof.

[0099] In another embodiment, the present disclosure provides a method for delivering a recombinant protein to a subject, the method comprising the step of contacting the subject with an RNA of the methods and compositions of the present disclosure, thereby delivering a recombinant protein to a subject.[000100] In another embodiment, a method of the present disclosure comprises increasing the number, percentage, or frequency of modified uridine nucleosides in the RNA molecule to decrease immunogenicity or increase efficiency of translation. In some embodiments, the number of modified uridine residues in an RNA, oligoribonucleotide, or polyribonucleotide molecule determines the magnitude of the effects observed in the present disclosure.[000101] In another embodiment, between 0.1% and 100% of the uridine residues in the modified RNAs of the methods and compositions of the present disclosure are modified (e.g. by the presence of pseudouridine). In another embodiment, 0.1% of the residues are modified. In another embodiment, 0.2%. In another embodiment, the fraction is 0.3%. In another embodiment, the fraction is 0.4%. In another embodiment, the fraction is 0.5%. In another embodiment, the fraction is 0.6%. In another embodiment, the fraction is 0.8%. In another embodiment, the fraction is 1%. In another embodiment, the fraction is 1.5%. In another embodiment, the fraction is 2%. In another embodiment, the fraction is 2.5%. In another embodiment, the fraction is 3%. In another embodiment, the fraction is 4%. In another embodiment, the fraction is 5%. In another embodiment, the fraction is 6%. In another embodiment, the fraction is 8%. In another embodiment, the fraction is 10%. In another embodiment, the fraction is 12%. In another embodiment, the fraction is 14%. In another embodiment, the fraction is 16%. In another embodiment, the fraction is 18%. In another embodiment, the fraction is 20%. In anotherP-639811-PC embodiment, the fraction is 25%. In another embodiment, the fraction is 30%. In another embodiment, the fraction is 35%. In another embodiment, the fraction is 40%. In another embodiment, the fraction is 45%. In another embodiment, the fraction is 50%. In another embodiment, the fraction is 60%. In another embodiment, the fraction is 70%. In another embodiment, the fraction is 80%. In another embodiment, the fraction is 90%. In another embodiment, the fraction is 100%.[000102] In another embodiment, the fraction is less than 5%. In another embodiment, the fraction is less than 3%. In another embodiment, the fraction is less than 1%. In another embodiment, the fraction is less than 2%. In another embodiment, the fraction is less than 4%. In another embodiment, the fraction is less than 6%. In another embodiment, the fraction is less than 8%. In another embodiment, the fraction is less than 10%. In another embodiment, the fraction is less than 12%. In another embodiment, the fraction is less than 15%. In another embodiment, the fraction is less than 20%. In another embodiment, the fraction is less than 30%. In another embodiment, the fraction is less than 40%. In another embodiment, the fraction is less than 50%. In another embodiment, the fraction is less than 60%. In another embodiment, the fraction is less than 70%.[000103] In another embodiment, 0.1% of the residues of a given uridine nucleotide are modified. In another embodiment, the fraction of the nucleotide is 0.2%. In another embodiment, the fraction is 0.3%. In another embodiment, the fraction is 0.4%. In another embodiment, the fraction is 0.5%. In another embodiment, the fraction is 0.6%. In another embodiment, the fraction is 0.8%. In another embodiment, the fraction is 1%.In another embodiment, the fraction is 1.5%. In another embodiment, the fraction is 2%.In another embodiment, the fraction is 2.5%. In another embodiment, the fraction is 3%.In another embodiment, the fraction is 4%. In another embodiment, the fraction is 5%. In another embodiment, the fraction is 6%. In another embodiment, the fraction is 8%. In another embodiment, the fraction is 10%. In another embodiment, the fraction is 12%. In another embodiment, the fraction is 14%. In another embodiment, the fraction is 16%. In another embodiment, the fraction is 18%. In another embodiment, the fraction is 20%. In another embodiment, the fraction is 25%. In another embodiment, the fraction is 30%. InP-639811-PC another embodiment, the fraction is 35%. In another embodiment, the fraction is 40%. In another embodiment, the fraction is 45%. In another embodiment, the fraction is 50%. In another embodiment, the fraction is 60%. In another embodiment, the fraction is 70%. In another embodiment, the fraction is 80%. In another embodiment, the fraction is 90%. In another embodiment, the fraction is 100%.[000104] In another embodiment, the fraction of the given uridine nucleotide is less than 8%. In another embodiment, the fraction is less than 10%. In another embodiment, the fraction is less than 5%. In another embodiment, the fraction is less than 3%. In another embodiment, the fraction is less than 1%. In another embodiment, the fraction is less than 2%. In another embodiment, the fraction is less than 4%. In another embodiment, the fraction is less than 6%. In another embodiment, the fraction is less than 12%. In another embodiment, the fraction is less than 15%. In another embodiment, the fraction is less than 20%. In another embodiment, the fraction is less than 30%. In another embodiment, the fraction is less than 40%. In another embodiment, the fraction is less than 50%. In another embodiment, the fraction is less than 60%. In another embodiment, the fraction is less than 70%.[000105] In some embodiments, the mRNA molecules described herein comprise one or more modified nucleotides. In some embodiments, the at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the uracil nucleotides in the mRNA are modified.[000106] In some embodiments, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the uracil nucleotides in the ORF are modified.[000107] In some embodiments, the modification is selected from the group consisting of pseudouridine, Nl-methylpseudouridine, 2-thiouridine, 4'-thiouridine, 5- methylcytosine, 2-thio-l-methyl-l-deaza-pseudouridine, 2-thio-l-methyl-pseudouridine, 2-thio-5- aza-uridine, 2-thio-dihydropseudouridine, 2-thio-dihydrouridine, 2-thio- pseudouridine, 4-methoxy- 2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-l-P-639811-PC methyl-pseudouridine, 4-thio- pseudouridine, 5-aza-uridine, dihydropseudouridine, 5- methyluridine, 5-methyluridine, 5- methoxyuridine, and 2'-0-methyl uridine.[000108] In some embodiments, the modification is Nl- methylpseudouridine.Codon Optimization[000109] In some embodiments, the mRNA molecules may be codon optimized. Proteins of the present disclosure may also be codon optimized by methods known in the art, for example, to improve their expression.[000110] In some embodiments, codon-optimization refers to alteration of codons in a coding region of a nucleic acid molecule (e.g., a nucleotide sequence) to reflect the typical codon usage of a host organism (e.g., a subject receiving a nucleic acid molecule (e.g., a nucleotide sequence)) preferably without altering the amino acid sequence encoded by the nucleic acid molecule. In some embodiments, coding regions are codon- optimized for optimal expression in a subject to be treated using the RNA molecules described herein. In some embodiments, codon-optimization may be performed such that codons for which frequently occurring tRNAs are available are inserted in place of "rare codons."[000111] A given amino acid can be replaced by a residue having similar physiochemical characteristics, e.g., substituting one aliphatic residue for another (such as lie, Vai, Leu, or Ala for one another), or substitution of one polar residue for another (such as between Lys and Arg; Glu and Asp; or Gin and Asn). Other such conservative substitutions, e.g., substitutions of entire regions having similar hydrophobicity characteristics, are well known. Polypeptides comprising conservative amino acid substitutions can be tested to confirm that the desired activity of the polypeptide is retained.[000112] In some embodiments, a polynucleotide (e.g., a polyribonucleotide or a nucleotide sequence) of the present disclosure is codon optimized, wherein the codons in the polynucleotide (e.g., the polyribonucleotide) are adapted to human codon usage.P-639811-PC[000113] Amino acids can be grouped according to similarities in the properties of their side chains (in A. L. Lehninger, in Biochemistry, second ed., pp. 73-75, Worth Publishers, New York (1975)): (1) non-polar: Ala (A), Vai (V), Leu (L), lie (I), Pro (P), Phe (F), Trp (W), Met (M); (2) uncharged polar: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N), Gin (Q); (3) acidic: Asp (D), Glu (E); (4) basic: Lys (K), Arg (R), His (H).[000114] Alternatively, naturally occurring residues can be divided into groups based on common side-chain properties: (1) hydrophobic: Norleucine, Met, Ala, Vai, Leu, lie; (2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5) residues that influence chain orientation: Gly, Pro; (6) aromatic: Trp, Tyr, Phe. Non-conservative substitutions entail exchanging a member of one of these classes for another class.[000115] Particular conservative substitutions include, for example; Ala into Gly or into Ser; Arg into Lys; Asn into Gin or into H is; Asp into Glu; Cys into Ser; Gin into Asn; Glu into Asp; Gly into Ala or into Pro; His into Asn or into Gin; lie into Leu or into Vai; Leu into lie or into Vai; Lys into Arg, into Gin or into Glu; Met into Leu, into Tyr or into lie; Phe into Met, into Leu or into Tyr; Ser into Thr; Thr into Ser; Trp into Tyr; Tyr into Trp; and / or Phe into Vai, into lie or into Leu.5' cap[000116] In some embodiments, a mRNA molecule described herein comprises a 5' cap. In some embodiments, the 5' cap is a 7-methylguanosine cap (also known as "m7G" or "Cap-0"), comprising a guanosine that is linked through a 5' - 5' - triphosphate bond to the first transcribed nucleotide. In some embodiments, the mRNA comprises a 5' cap selected from the group consisting of 3'-O-Me-m7G(5')ppp(5')G (the ARCA cap), G(5')ppp(5')A, G(5')ppp(5')G, m7G(5')ppp(5')A, m7G(5')ppp(5')G, m7G(5,)ppp(5,)(2,OMeA)pG, m7G(5,)ppp(5,)(2,OMeA)pU, and m7G(5')ppp(5')(2'OMeG)pG.[000117] In some embodiments, the 5'-cap is a structure found on the 5'-end of an RNA, e.g., mRNA, and generally includes a guanosine nucleotide connected to an RNA,P-639811-PC e.g., mRNA, via a 5'- to 5'-triphosphate linkage (also referred to as Gppp or G(5')ppp(5')). In some embodiments, a guanosine nucleoside included in a 5' cap may be modified, for example, by methylation at one or more positions (e.g., at the 7-position) on a base (guanine), and / or by methylation at one or more positions of a ribose. In some embodiments, a guanosine nucleoside included in a 5' cap comprises a 3'0 methylation at a ribose (3'0MeG). In some embodiments, a guanosine nucleoside included in a 5' cap comprises methylation at the 7-position of guanine (m7G). In some embodiments, a guanosine nucleoside included in a 5' cap comprises methylation at the 7'-position of guanine and a 3' 0 methylation at a ribose (m7(3'OMeG)).[000118] In some embodiments, the 5'-cap structure is a capO (methylation of the first nucleobase, e.g., m7GpppN), capl (additional methylation of the ribose of the adjacent nucleotide of m7GpppN), cap2 (additional methylation of the ribose of the 2nd nucleotide downstream of the m7GpppN), cap3 (additional methylation of the ribose of the 3rd nucleotide downstream of the m7GpppN), cap4 (additional methylation of the ribose of the 4th nucleotide downstream of the m7GpppN), ARCA ("anti-reverse cap analogue"), modified ARCA (e.g. phosphothioate modified ARCA), inosine, N1 -methylguanosine, 2'-fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino- guanosine, LNA-guanosine, and 2-azido-guanosine.5' UTR and 3' UTR[000119] In some embodiments, the mRNA molecules described herein comprise at least one UTR (Untranslated Region). In some embodiments, the mRNA molecules comprise at least one 5' untranslated region (5' UTR) and / or at least one 3' untranslated region (3' UTR). In some embodiments, the mRNA molecules comprise at least one 5' untranslated region (5' UTR). In some embodiments, the mRNA molecules comprise at least one 3' untranslated region (3' UTR). In some embodiments, the mRNA molecules comprise at least one 5' untranslated region (5' UTR), at least one 3' untranslated region (3' UTR), and at least one polyadenylation (poly(A)) sequence.P-639811-PC[000120] In some embodiments, the UTR (Untranslated Region) comprises sequences of nucleotides that are at the 5' and 3' ends of a mRNA molecule which are not translated. In some embodiments, the 5' UTR influences mRNA stability and translation efficiency. In some embodiments, the 5' UTR contains elements that help ribosomes identify the start codon. In some embodiments, the 5' UTR starts at the transcription start site and continues to the start codon but does not include the start codon.[000121] In some embodiments, the "untranslated region" or "UTR" is commonly used in the art to refer to a region in a DNA molecule which is transcribed but is not translated into an amino acid sequence, or to the corresponding region in an RNA polynucleotide, such as an mRNA molecule. An untranslated region (UTR) can be present 5' (upstream) of an open reading frame (5' UTR) and / or 3' (downstream) of an open reading frame (3' UTR). In some embodiments, the "five prime untranslated region" or "5' UTR" refer to a sequence of a nucleotide sequence between the 5' end of the nucleotide sequence (e.g., a transcription start site) and a start codon of a coding region of the nucleotide sequence. In some embodiments, "5' UTR" refers to a sequence of a nucleotide sequence that begins at the 5' end of the nucleotide sequence (e.g., a transcription start site) and ends one nucleotide (nt) before a start codon (usually AUG) of a coding region of the nucleotide sequence, e.g., in its natural context. In some embodiments, a 5' UTR comprises a Kozak sequence. A 5' UTR is downstream of the 5'- cap (if present), e.g., directly adjacent to the 5'-cap. In some embodiments, a 5' UTR disclosed herein comprises a cap proximal sequence, e.g., as defined and described herein. In some embodiments, a cap proximal sequence comprises a sequence adjacent to a 5' cap.In some embodiments, an RNA utilized in accordance with the present disclosure comprises a 3' UTR. As used herein, the terms "three prime untranslated region," "3' untranslated region," or "3' UTR" refer to a sequence of an mRNA molecule that begins following a stop codon of a coding region of an open reading frame sequence. In some embodiments, the 3' UTR begins immediately after a stop codon of a coding region of an open reading frame sequence, e.g., in its natural context. In other embodiments, the 3'P-639811-PCUTR does not begin immediately after stop codon of the coding region of an open reading frame sequence, e.g., in its natural context. The term "3' UTR" preferably does not include the poly(A) sequence. Thus, the 3' UTR is upstream of the poly(A) sequence (if present), e.g. directly adjacent to the poly(A) sequence. For example, disclosed sequences can include regions preceding and following the coding region, e.g., 5' untranslated region (5' UTR) or "leader" sequences and 3' UTR or "trailer" sequences, as well as intervening sequences (introns) between individual coding segments (exons). It will be appreciated that the disclosed mRNA sequences may include one or more stop codons, e.g., placed between the de-epitoped Ara h 1 or 2 sequence and the 3' UTR.[000122] In some embodiments, the 3' UTR controls mRNA stability, localization, and translation. In some embodiments, the 3' UTR starts immediately following the stop codon and continues until the transcriptional termination signal. In some embodiments, UTRs are associated with processes of mRNA translation, and by interacting with RNA- binding proteins and microRNAs, UTRs can influence mRNA's translation efficiency and resistance to degradation.[000123] In some embodiments, the mRNA molecule disclosed herein comprises a 5' and / or 3' heterologous UTR, which is derived from the UTRs of the mRNA transcript (i.e., the UTRs of Ara h 1 or Ara h 2 genes). In some embodiments, the mRNA comprises the 3' UTR of Ara h 1. In some embodiments, the mRNA comprises the 5' UTR of Ara h 1. In some embodiments, the mRNA comprises the 3' UTR of Ara h 2. In some embodiments, the mRNA comprises the 5' UTR of Ara h 2.[000124] In some embodiments, the first and second mRNA molecules comprise at least one 5' untranslated region (5' UTR), at least one 3' untranslated region (3' UTR), and at least one polyadenylation (poly(A)) sequence.[000125] In some embodiments, the 5' UTR comprises the nucleic acid sequence of HBB 5' UTR hemoglobin subunit beta from Homo sapiens. In some embodiments, the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 8.[000126] In some embodiments, the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 8, or a sequence having at least 85%, preferably at least 90%, more preferablyP-639811-PC at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the 5' UTR comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 8.In some embodiments, the 5' UTR comprises the nucleic acid sequence of HBB 5' UTR hemoglobin subunit beta from Homo sapiens. In some embodiments, the 5' UTR further comprises a 'flank sequence', e.g., which is not part of the natural UTR added for efficient in vitro transcription (IVT) of template DNA to mRNA. In some embodiments, the 'flank sequence' comprises the nucleic acid sequence of AGGAAAT. In some embodiments, the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 15.[000127] In some embodiments, the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 15, or a sequence having at least 85%, preferablyat least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the 5' UTR comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 15.[000128] In some embodiments, the 5' UTR further comprises the nucleic acid sequence of AGGAAAT. In some embodiments, the 5' UTR further comprises the nucleic acid sequence of AGGAAAT, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the 5' UTR comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence AGGAAAT.[000129] In some embodiments, the 3' UTR comprises the nucleic acid sequence of HBA1 3' UTR hemoglobin subunit alpha 1 from Homo sapiens. In some embodiments, the 3' UTR comprises the nucleic acid sequence of NCBI Reference NM_000558.5. In some embodiments, the 3' UTR comprises the nucleic acid sequence of HBB 3' UTR hemoglobin subunit beta from Homo sapiens. In some embodiments, the 3' UTR comprises the nucleic acid sequence of SEQ ID NO: 9 or SEQ ID NO: 10. In some embodiments, the 3' UTR comprises the nucleic acid sequence of SEQ ID NO: 9. In some embodiments, the 3' UTR comprises the nucleic acid sequence of SEQ ID NO: 10.P-639811-PC[000130] In some embodiments, the 3' UTR comprises the nucleic acid sequence of SEQ ID NO: 9, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the 5' UTR comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 9.[000131] In some embodiments, the 3' UTR comprises the nucleic acid sequence of SEQ ID NO: 10, or a sequence having at least 85%, preferablyat least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the 5' UTR comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 10.[000132] In some embodiments, the mRNA molecules described herein comprise at least one signal sequence. The term "signal sequence" may encompass a sequence which encodes a "signal peptide" which is a short sequence of amino acids at the N-terminus of a protein that directs the protein to the endoplasmic reticulum (ER). In some embodiments, the signal peptide has a role in protein expression and folding, and can help direct the protein to secretory pathways. In some embodiments, the signal peptide is the Osteonectin (also known as SPARC or BM-40) secretory signal peptide, which allows proteins to be exported from the cytosol. In some embodiments, during translocation from the cytosol the signal peptide is removed from the protein by endogenous proteases.[000133] In some embodiments, the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7. In some embodiments, the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 6. In some embodiments, the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 7.[000134] In some embodiments, the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 6, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the signal sequence comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 6.P-639811-PC[000135] In some embodiments, the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 7, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the signal sequence comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 7.[000136] In some embodiments, the signal sequence encodes the signal peptide comprising the amino acid sequence of SEQ ID NO: 5. In some embodiments, the signal sequence encodes a signal peptide comprising the amino acid sequence of GenBank NO: AAA60993.1. In some embodiments, the signal sequence comprises a nucleic acid sequence encoding SEQ ID NO: 5. In some embodiments, the signal sequence comprises a nucleic acid sequence encoding SEQ ID NO: 5, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the signal sequence comprises the nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 5.[000137] In some embodiments, mRNA molecules described herein comprise a nucleotide sequence that encodes a 5'UTR and / or a 3' UTR. In some embodiments, mRNA molecules described herein comprise a nucleotide sequence that encodes a polyA tail. In some embodiments, mRNA molecules described herein comprise a 5' cap, which may be incorporated during transcription, or joined to a nucleotide sequence post -transcription.PolyA Tail[000138] In some embodiments, a polynucleotide (e.g., DNA, RNA) disclosed herein comprises a polyadenylate (polyA) sequence, e.g., as described herein. In some embodiments, a polyA sequence is situated downstream of a 3' UTR, e.g., adjacent to a 3' UTR.[000139] In some embodiments, the mRNA molecules described herein comprise at least one polyadenylation (poly(A)) sequence or poly(A) tail. In some embodiments, the mRNA molecules comprise a poly(A) tail.P-639811-PC[000140] In some embodiments, the terms "poly(A) sequence", "poly(A) tail", and "poly(A) region" refer to a sequence of adenosine nucleotides at the 3' end of the mRNA molecule. The poly(A) tail may confer stability to the mRNA and protect it from exonuclease degradation. The poly(A) tail may enhance translation. In some embodiments, the poly(A) tail is essentially homopolymeric. In some embodiments, the poly(A) tail comprises between about 10 to about 500 adenosine nucleotides, about 10 to about 200 adenosine nucleotides, about 40 to about 200 adenosine nucleotides, or about 40 to about 150 adenosine nucleotides. In some embodiments, the length of the poly(A) tail may be at least about 10, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, or 500 adenosine nucleotides.[000141] In some embodiments, a poly(A) sequence in accordance with the present disclosure is not limited to a particular length. In some embodiments, a poly(A) sequence is any length. In some embodiments, a poly(A) sequence comprises, essentially consists of, or consists of at least 20, at least 30, at least 40, at least 80, or at least 100 and up to 500, up to 400, up to 300, up to 200, or up to 150 A nucleotides, and, in particular, about 120 A nucleotides. In this context, "essentially consists of" means that most nucleotides in the poly(A) sequence, typically at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% by number of nucleotides in the poly(A) sequence are A nucleotides, but permits that remaining nucleotides are nucleotides other than A nucleotides, such as U nucleotides (uridylate), G nucleotides (guanylate), or C nucleotides (cytidylate). In this context, "consists of" means that all nucleotides in the poly(A) sequence, i.e., 100% by number of nucleotides in the poly(A) sequence, are A nucleotides. The term "A nucleotide" or "A" refers to adenylate. [000142] In some embodiments, a poly(A) sequence comprises a specific number of adenosines, such as about 50 or more, about 60 or more, about 70 or more, about 80 or more, about 90 or more, about 100 or more, about 120, or about 150 or about 200. In some embodiments a poly(A) sequence of an RNA may comprise 200 A residues or less. In some embodiments, a poly(A) sequence of an RNA may comprise about 200 A residues. In some embodiments, a poly(A) sequence of an RNA may comprise 180 A residues orP-639811-PC less. In some embodiments, a poly(A) sequence of an RNA may comprise about 180 A residues. In some embodiments, a poly(A) sequence may comprise 150 residues or less.[000143] In some embodiments, the poly(A) sequence comprises a poly(A) tail from Simian virus 40 (SV40) late gene, the bovine growth hormone (BGH) polyadenylation signal, or the minimal rabbit f3-globin (mRBG) gene. In some embodiments, the polyadenylation signal is SV40 polyadenylation signal.[000144] The mRNAs disclosed herein may be synthesized according to any of a variety of methods. A skilled artisan is familiar with the methods and techniques for in- vitro transcription of the mRNA molecules described herein.[000145] In some embodiments, the mRNA molecules described herein further comprise one or more "enhancer sequences" to assist in elevating gene expression. Such enhancers are known in the art. By including an enhancer sequence, the expression of the selected protein may be enhanced. These enhancers are often found 5' to the start of transcription, but can be inserted in the forward or reverse orientation 5' or 3' to the coding sequence. In some instances, these 5' enhancing elements are introns.[000146] In some embodiments, the mRNA molecule(s) encoding de-epitoped Ara h 1 are encapsulated in the LNP described herein in detail. In some embodiments, the mRNA molecule(s) encoding de-epitoped Ara h 2 are encapsulated in the LNP described herein in detail. In some embodiments, the mRNA molecules encoding de-epitoped Ara h 1 and mRNA molecules encoding de-epitoped Ara h 2 are encapsulated in the LNP described herein in detail. In some embodiments, the LNP encapsulates at least one mRNA molecule encoding de-epitoped Ara h 1. In some embodiments, the LNP encapsulates at least one mRNA molecule encoding de-epitoped Ara h 2. In some embodiments, the LNP encapsulates at least one mRNA molecule encoding de-epitoped Ara h 1 and at least one mRNA molecule encoding de-epitoped Ara h 2. In some embodiments, the LNP encapsulates one mRNA molecule encoding de-epitoped Ara h 1 and one mRNA molecule encoding de-epitoped Ara h 2. . In some embodiments, the LNP encapsulates at least one mRNA molecule encoding de-epitoped Ara h 1 and encoding de-epitoped Ara h 2.P-639811-PCLNP (Lipid Nanoparticle)[000147] In some embodiments, the present disclosure relates to Lipid Nanoparticles (LNPs). In some embodiments, the LNPs are for delivering mRNA vaccines in vivo. A skilled artisan would appreciate that an LNP is a particle, e.g., a spherical particle, composed of lipids that can encapsulate and deliver mRNA or other therapeutic molecules. In some embodiments, the LNP protects the mRNA from degradation and facilitates its delivery to cells. In some embodiments, the LNP is designed to fuse with a cell membrane, allowing the mRNA to enter cells.[000148] In some embodiments, disclosed herein is a lipid nanoparticle encapsulating the de-epitoped Ara h 1 mRNA and a de-epitoped Ara h 2 mRNA. In some embodiments, disclosed herein is a lipid nanoparticle encapsulating the a) de-epitoped Ara h 1 mRNA selected from SEQ ID NO 17 or 19, and b) a de-epitoped Ara h 2 mRNA selected from SEQ ID NO 18 and 20.[000149] In some embodiments, the weight ratio of the de-epitoped Ara h l and the mRNA molecule encoding de-epitoped Ara h 2 in the lipid nanoparticle is about 1:1 (w:w). [000150] In some embodiments, the LNP comprises a cationic lipid. In some embodiments, the LNP comprises a polyethylene glycol (PEG)-conjugated lipid. In some embodiments, the LNP comprises a cholesterol- based lipid. In some embodiments, the cholesterol- based lipid comprises cholesterol. In some embodiments, the LNP comprises a mixture of one or more lipids selected from the group consisting of a cationic lipid, a polyethylene glycol (PEG)-conjugated lipid, a cholesterol- based lipid, and other lipids.[000151] In some embodiments, the LNP comprises one or more lipids selected from the group consisting of l,2-dioleoyl-SN-glycero-3- phosphoethanolamine (DOPE); 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC); 1,2- dioleoyl-sn-glycero-3-phospho-L- serine (DO PS); l,2-dielaidoyl-sn-glycero-3- phosphoethanolamine (DEPE); and 1,2-dioleoyl- sn-glycero-3-phosphocholine (DPOC), dipalmitoylphosphatidylcholine (DPPC), 1,2- dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1.2-Distearoylphosphatidylethanolamine (DSPE), and l,2-dilauroyl-sn-glycero-3-phosphoethanolamine (DLPE),P-639811-PC dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl -phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4- (N-maleimidomethyl)-cyclohexane-l-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), phosphatidylserine, sphingolipids, cerebrosides, gangliosides, 16-0-monomethyl PE, 16-O-dimethyl PE, 18-1 - trans PE, and l-stearoyl-2-oleoyl-phosphatidyethanolamine (SOPE).[000152] In some embodiments, the LNP comprises l,2-distearoyl-sn-glycero-3- phosphocholine (DSPC). In some embodiments, the LNP comprises [(4- hydroxybutyl)azanediyl]di(hexane-6,l-diyl) bis(2-hexyldecanoate) (ALC-0315, Acuitas Therapeutics). In some embodiments, the LNP comprises a PEGylated lipid (e.g. ALC-0159). In some embodiments, the LNP comprises Methoxypolyethyleneglycoloxy(2000)-N,N- ditetradecylacetamide. In some embodiments, the LNP comprises cholesterol and 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC). In some embodiments, the LNP comprises [(4-hydroxybutyl)azanediyl]di(hexane-6,l-diyl) bis(2-hexyldeca noate),Methoxypolyethyleneglycoloxy(2000)-N,N-ditetradecylacetamide, cholesterol and 1,2- distearoyl-sn-glycero-3-phosphocholine in the molar ratio 47.5 : 1.8 : 40.7 : 10. In some embodiments, the LNP comprises ALC-0315, ALC-0159, cholesterol and DSPC in the molar ratio of a bout 47.5 : 1.8 : 40.7 : 10.[000153] In some embodiments, the lipid nanoparticle comprises [(4- hydroxybutyl)azanediyl]di(hexane-6,l-diyl) bis(2-hexyldeca noate),(Methoxypolyethyleneglycoloxy(2000)-N,N-ditetradecylacetamide), cholesterol, and 1,2- distearoyl-sn-glycero-3-phosphocholine.[000154] In some embodiments, the LNP has a mean diameter of from about 30 nm to about 150 nm, from about 40 nm to about 150 nm, from about 50 nm to about 150 nm, from about 60 nm to about 130 nm, from about 70 nm to about 110 nm, from about 70 nm to about 100 nm, from about 80 nm to about 100 nm, from about 90 nm to about 100 nm, from about 70 to about 90 nm, from about 80 nm to about 90 nm, from about 70 nm to about 80 nm, or about 30 nm, 35 nm, 40 nm, 45 nm, 50 nm, 55 nm, 60 nm, 65 nm, 70 nm,P-639811-PC75 nm, 80 nm, 85 nm, 90 nm, 95 nm, 100 nm, 105 nm, 110 nm, 115 nm, 120 nm, 125 nm, 130 nm, 135 nm, 140 nm, 145 nm, or 150 nm, and is substantially non-toxic.[000155] In some embodiments, the LNPs described herein are comprised in a formulation (the LNP formulation). In some embodiments, the LNP formulation comprises a plurality of LNPs and a stabilizing agent. In some embodiments, the LNP formulation comprises a plurality of LNPs and a cryoprotectant. In some embodiments, the LNP formulation comprises a plurality of LNPs and an antioxidant.[000156] In some embodiments, the cryoprotectant is for improved LNP stability. In some embodiments, the cryoprotectant is for improved LNP in vivo performance. In some embodiments, the cryoprotectant is for improved LNP stability after freeze-drying. In some embodiments, the cryoprotectant is for improved LNP stability after long storage. In some embodiments, the cryoprotectant is for improved LNP stability after storage at -20C. In some embodiments, the cryoprotectant is for improved LNP stability after storage at -80C. In some embodiments, the cryoprotectant is for improved LNP stability after storage at 4C. [000157] In some embodiments, the cryoprotectant is for extended shelf life of the LNPs. In some embodiments, the cryoprotectant is selected from a polyol, a nondetergent sulfobetaine, an osmolyte, a PEG, a polyvinylpyrrolidone, pentaerythritol propoxylate, or polypropylene glycol P 400, an organic solvent, a sugar, and a salt. In some embodiments, the cryoprotectant is selected from glycerol, sucrose, trehalose, mannitol, propylene glycol, or any combination thereof. In some embodiments, the cryoprotectant is glycerol. In some embodiments, the cryoprotectant is sucrose. In some embodiments, the cryoprotectant is trehalose. In some embodiments, the cryoprotectant is mannitol. In some embodiments, the cryoprotectant is propylene glycol.[000158] The LNPs described herein can be prepared by various techniques presently known in the art. A skilled artisan is familiar with the methods and techniques for preparing LNPs. An artisan is also familiar with the methods for preparing mRNA-loaded LNPs (also known as "loading" or "encapsulation").[000159] In some embodiments, the LNP comprises a messenger RNA (mRNA) molecule comprising an open reading frame (ORF) encoding de-epitoped Ara h 1. In someP-639811-PC embodiments, the LNP comprises a messenger RNA (mRNA) molecule comprising an ORF encoding de-epitoped Ara h 2. In some embodiments, the LNP comprises a messenger RNA (mRNA) molecule comprising an open reading frame (ORF) encoding de-epitoped Ara h 2 and an ORF encoding de-epitoped Ara h 2. In some embodiments, all mRNA structural elements required for protein translation, e.g., UTRs, and secretion of the protein from the cytosol, e.g., nucleic acid encoding a signal peptide, are included for each ORF.[000160] In some embodiments, the LNP comprises a first messenger RNA (mRNA) molecule comprising an open reading frame (ORF) encoding de-epitoped Ara h 1 and a second mRNA molecule comprising an ORF encoding and de-epitoped Ara h 2.[000161] In some embodiments, the LNP comprises at least one mRNA molecule comprising an ORF encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof. In some embodiments, the LNP comprises at least one mRNA molecule comprising an ORF encoding de-epitoped Ara h 1. In some embodiments, the LNP comprises at least one mRNA molecule comprising an ORF encoding de-epitoped Ara h 2. In some embodiments, the LNP comprises at least one mRNA molecule comprising an ORF encoding de-epitoped Ara h 1 and de-epitoped Ara h 2. In some embodiments, the LNP comprises at least one mRNA molecule comprising an ORF encoding de-epitoped Ara h 1 and at least one mRNA molecule comprising an ORF encoding de-epitoped Ara h 2.[000162] As used herein, "de-epitoped Ara h 1" or "DE-Ara h 1" refers to a modified Ara h 1 that has reduced or abolished binding with anti-Ara h 1 antibodies, e.g., to anti-Ara h 1 IgE antibodies (as compared to antibody binding to the wild-type Ara h 1) due to mutation(s) at one or more epitopes recognized by the anti-Ara h 1 antibodies. In one embodiment, the de-epitoped Ara h 1 has reduced allergenicity as compared to its wildtype counterpart.[000163] As used herein, "de-epitoped Ara h 2" or "DE-Ara h 2" refers to a modified Ara h 2 that has reduced or abolished binding with anti-Ara h 2 antibodies, e.g., to anti-Ara h 2 IgE antibodies (as compared to antibody binding to the wild-type Ara h 2) due to mutation(s) at one or more epitopes recognized by the anti-Ara h 2 antibodies. In oneP-639811-PC embodiment, the de-epitoped Ara h 2 has reduced allergenicity as compared to its wildtype counterpart.[000164] As used herein, an "epitope" refers to the part of a macromolecule (e.g., Ara h 1, or Ara h 2 allergen) that is bound by an antibody or an antigen-binding fragment thereof. There are two types of epitopes in a protein sequence: linear epitopes, which are linear amino acid sequences bound by antibodies, and discontinuous epitopes (also called "conformational epitopes"), which exist only when the protein is folded into a particular fold.[000165] As used herein, an "allergen" refers to a substance, protein, or nonprotein, capable of inducing allergy or specific hypersensitivity.[000166] As used herein, "allergenicity" or "allergenic" refers to the ability of an antigen or allergen to induce an abnormal immune response, which is an overreaction and different from a normal immune response in that it does not result in a protective / prophylaxis effect but instead causes physiological function disorder or tissue damage.[000167] As used herein, "hypoallergenic" refers to a substance having little or reduced likelihood of causing an allergic response.[000168] In some embodiments, the LNPs described herein are used for inducing desensitization to peanuts and / or immuno modulation of a response to peanuts in a subject allergic to peanuts.[000169] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleotide sequence set forth in SEQ ID NO: 2, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleotide sequence set forth in SEQ ID NO: 2, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 1 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 2.P-639811-PC[000170] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 4, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 4, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 2 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 4.[000171] In some embodiments, de-epitoped Ara h 1 comprises an amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the de-epitoped Ara h 1 comprises the amino acid sequence set forth in SEQ ID NO: 1, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 1. In some embodiments, the de-epitoped Ara h 1 comprises an amino acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 1.[000172] In some embodiments, de-epitoped Ara h 2 comprises an amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the de-epitoped Ara h 2 comprises the amino acid sequence set forth in SEQ ID NO: 3, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 3. In some embodiments, the de-epitoped Ara h 2 comprises an amino acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 3.[000173] In some embodiments, de-epitoped Ara h 2 comprises an amino acid sequence set forth in SEQ ID NO: 21. In some embodiments, the de-epitoped Ara h 2 comprises the amino acid sequence set forth in SEQ ID NO: 21, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 21. In some embodiments, the de-epitoped Ara h 2 comprises an amino acid sequence that is atP-639811-PC least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 21.[000174] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises a nucleic acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 18 or 20. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 2 comprises the nucleic acid sequence set forth in SEQ ID NO: 18, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 2 comprises the nucleic acid sequence set forth in SEQ ID NO: 20, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 20.[000175] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises a nucleic acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 17 or 19. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 1 comprises the nucleic acid sequence set forth in SEQ ID NO: 17, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 17. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 1 comprises the nucleic acid sequence set forth in SEQ ID NO: 19, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 19.[000176] In some embodiments, disclosed herein is a lipid nanoparticle encapsulating the de-epitoped Ara h 1 mRNA and a de-epitoped Ara h 2 mRNA described herein. In some embodiments, the de-epitoped Ara h 1 mRNA comprises: (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de- epitoped Ara h 1 comprising the nucleic acid sequence of SEQ ID NO: 2 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or aP-639811-PC fragment or variant thereof. In some embodiments, the de-epitoped Ara h 1 mRNA comprises: (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof;(ii) an ORF encoding de-epitoped Ara h 1 comprising the amino acid sequence of SEQ ID NO: 1 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof. In some embodiments the mRNA molecule comprises (i) 5' untranslated region (5' UTR) having the nucleic acid sequence of SEQ ID NO: 8; (ii) a signal sequence comprising the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7; (iii) an ORF encoding de-epitoped Ara h 1 having the amino acid sequence of SEQ ID NO: 1; (iv) a 3' untranslated region (3' UTR) having the nucleic acid sequence of SEQ ID NO: 10; and (v) a poly(A) tail.[000177] In some embodiments, the de-epitoped Ara h 2 mRNA comprises: (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 2 comprising the nucleic acid sequence of SEQ ID NO: 4 or SEQ ID NO: 16 or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof. In some embodiments, the de- epitoped Ara h 2 mRNA comprises: (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 2 comprising the nucleic acid sequence of SEQ ID NO: 16, or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof. In some embodiments, the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de-epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 3 or a fragment or variant thereof; and(iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof. In some embodiments, the mRNA molecule comprises (i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof; (ii) an ORF encoding de- epitoped Ara h 2 comprising the amino acid sequence of SEQ ID NO: 21, or a fragment or variant thereof; and (iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.P-639811-PC mRNA Vaccine[000178] In some embodiments, the present disclosure relates to vaccines comprising the LNP described herein in detail. In some embodiments, the vaccine is used for inducing desensitization to peanuts in a subject, or reducing allergic reaction to peanuts in a subject.[000179] In some embodiments, disclosed herein is a vaccine comprising the lipid nanoparticle encapsulating the de-epitoped Ara h 1 mRNA and a de-epitoped Ara h 2 mRNA described herein. In some embodiments, disclosed herein is a vaccine comprising the de-epitoped Ara h 1 mRNA and a de-epitoped Ara h 2 mRNA described herein.[000180] As used herein, "mRNA Vaccine", "nucleic acid vaccine" or "nucleic acid composition" refer to a vaccine, a vaccine composition or a composition which includes the LNP described herein comprising mRNA molecules encoding a de-epitoped Ara h 2 and or de-epitoped Ara h 1. Said vaccines or compositions may comprise other substances and molecules which are required, or which are advantageous when said vaccine or compositions is administered to an individual (e.g., pharmaceutical excipients).Pharmaceutical composition[000181] In some embodiments, disclosed is a pharmaceutical composition comprising the LNP described herein in detail. In some embodiments, the present pharmaceutical compositions are used for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.[000182] In some embodiments, disclosed is a pharmaceutical composition comprising LNPs comprising mRNA molecules encoding de-epitoped Ara h 1. In some embodiments, disclosed is a pharmaceutical composition comprising LNPs comprising mRNA molecules encoding de-epitoped Ara h 2. In some embodiments, disclosed is a pharmaceutical composition comprising LNPs comprising mRNA molecules encoding de- epitoped Ara h 1 and LNPs comprising mRNA molecules encoding de-epitoped Ara h 2. In some embodiments, disclosed is a pharmaceutical composition comprising LNPs comprising mRNA molecules encoding de-epitoped Ara h 1 and mRNA moleculesP-639811-PC encoding de-epitoped Ara h 2. In some embodiments, the mRNA molecules encoding deepitoped Ara h 1 and de-epitoped Ara h 2 are encapsulated within the same LNP molecule and / or in different LNP molecules. In some embodiments, the composition comprises LNPs comprising at least one mRNA molecule encoding de-epitoped Ara h 1 and de- epitoped Ara h 2.[000183] In some embodiments, disclosed is a pharmaceutical composition comprising mRNA molecules encoding de-epitoped Ara h 1. In some embodiments, disclosed is a pharmaceutical composition comprising mRNA molecules encoding de- epitoped Ara h 2. In some embodiments, disclosed is a pharmaceutical composition comprising mRNA molecules encoding de-epitoped Ara h 1 and mRNA molecules encoding de-epitoped Ara h 2. In some embodiments, the UTRs, signal peptide and ORF of each de-epitoped Ara h l and de-epitoped Ara h 2 are part of the same mRNA molecule, resulting in two separate de-epitoped proteins following administration and translation in a mammalian cell. In one embodiment, the UTRs, signal peptide and ORF of de- epitoped Ara h 1 are positioned first on the mRNA molecule. In another embodiment, the UTRs, signal peptide and ORF of de-epitoped Ara h 2 are positioned first on the mRNA molecule. In some embodiments, the translated de-epitoped Ara h 1, comprising the signal sequence, comprises the amino acid sequence as set forth in SEQ ID NO: 11. In some embodiments, the translated de-epitoped Ara h 2, comprising the signal sequence, comprises the amino acid sequence as set forth in SEQ ID NO: 12. In some embodiments, the translated de-epitoped Ara h 1, comprising the signal sequence, has at least 80% identity to the amino acid sequence as set forth SEQ ID NO: 11. In some embodiments, the translated de-epitoped Ara h 2, comprising the signal sequence, has at least 80% identity to the amino acid sequence as set forth SEQ ID NO: 12.[000184] In some embodiments, disclosed herein is a pharmaceutically acceptable composition comprising a de-epitoped Ara h 1 mRNA molecule described herein and a de-epitoped Ara h 2 mRNA molecule described herein.P-639811-PC[000185] In some embodiments, the de-epitoped Ara h 1 mRNA molecule and the de-epitoped Ara h 2 mRNA molecule are present in a ratio of about 10:0.1 to about 0.1:10 (w / w).[000186] In some embodiments, the ratio between the mRNA encoding de-epitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 is about 1:1 (w:w).[000187] In some embodiments, disclosed herein is a pharmaceutical composition comprising the lipid nanoparticle described hereing and a pharmaceutically acceptable excipient.[000188] In some embodiments, the pharmaceutical composition comprises about lpg to lmg of the mixture of the de-epitoped Ara h 1 mRNA and the de-epitoped Ara h 2 mRNA.[000189] In some embodiments, the pharmaceutical composition comprises about between 10 pg to about 200 pg of the mixture of the de-epitoped Ara h 1 mRNA and the de-epitoped Ara h 2 mRNA. In some embodiments, the pharmaceutical composition comprises about 30 pg or 100 pg of the mixture of the de-epitoped Ara h 1 mRNA and the de-epitoped Ara h 2 mRNA.[000190] Administration of the mRNA vaccine or pharmaceutical composition described herein, can be carried out via any of the accepted modes of administration of agents for serving similar utilities. The mRNA vaccines or pharmaceutical compositions described herein, optionally further comprising relevant pharmaceutically active ingredients, such as carriers, diluents or excipients, may be formulated into preparations in liquid forms, such as solutions, injections, and inhalants. In addition, suitable excipients such as salts, buffers and stabilizers may be present within the composition. A skilled artisan would appreciate that the term "physiologically acceptable carrier, diluent or excipient", may in some embodiments, be used interchangeably with the term "pharmaceutically acceptable carrier" having all the same means and qualities.[000191] Administration may be achieved by different routes, including parenteral, nasal, intramuscular, intravenous, or topical. In some embodiments, the vaccine or composition described herein is administered intravenously. In some embodiments, theP-639811-PC vaccine or composition described herein is administered by portal vein administration. In some embodiments, the vaccine or composition described herein is administered by intramuscular administration.[000192] In some embodiments, the vaccine or composition is administered systemically. In some embodiments, the vaccine or composition is administered parenterally. In some embodiments, the composition is administered intravenously. In some embodiments, the vaccine or composition is administered intramuscularly. In some embodiments, the vaccine or composition is administered by subcutaneous injection.[000193] In some embodiments, the subject is a human subject. In some embodiments, the subject is a human child. In some embodiments, the subject is an adult human. In some embodiments, the subject is a non-human mammal.[000194] The vaccine or pharmaceutical composition may be administered alone or in combination with other known treatments. In some embodiments, the pharmaceutical composition is administered together with intravenous fluids.[000195] Typical routes of administration include, without limitation, systemic, intravenous, inhalation, parenteral, sublingual, buccal, and intranasal. The term parenteral as used herein includes subcutaneous injections, intravenous, intramuscular, intrasternal injection or infusion techniques. Pharmaceutical compositions according to some embodiments as described herein, are formulated so as to allow the active ingredients contained therein to be bioavailable upon administration of the composition to a patient.[000196] In a composition intended to be administered by injection or infusion, one or more of a surfactant, preservative, wetting agent, dispersing agent, suspending agent, buffer, stabilizer and isotonic agent may be included.[000197] The liquid pharmaceutical compositions, whether they be solutions, suspensions or other like form, may include one or more of the following adjuvants: sterile diluents such as water for injection, saline solution, preferably physiological saline, Ringer's solution, isotonic sodium chloride, fixed oils such as synthetic mono or diglycerides which may serve as the solvent or suspending medium, polyethylene glycols,P-639811-PC glycerin, propylene glycol or other solvents; antibacterial agents such as benzyl alcohol or methyl paraben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic. An injectable pharmaceutical composition is preferably sterile.[000198] The vaccines or pharmaceutical compositions may be prepared by methodology well known in the pharmaceutical art. For example, a pharmaceutical composition intended to be administered by injection or infusion can be prepared with one or more of salts, buffers and / or stabilizers, with sterile, distilled water so as to form a solution. A surfactant may be added to facilitate the formation of a homogeneous solution or suspension. Surfactants are compounds that non-covalently interact with the active ingredients so as to facilitate dissolution or homogeneous suspension of the active ingredients in the aqueous delivery system.[000199] The vaccines or pharmaceutical compositions may be administered in a therapeutically effective amount, which varies depending upon a variety of factors including the activity of the specific compound employed; the metabolic stability and length of action of the compound; the age, body weight, general health, sex, and diet of the patient; the mode and time of administration; the rate of excretion; the drug combination; the severity of the disease; and the subject undergoing therapy.[000200] A pharmaceutically acceptable carrier may be liquid, semi-liquid or solid. Solutions or suspensions used for parenteral, intradermal, subcutaneous or topical application may include, for example, a sterile diluent (such as water), saline solution, fixed oil, polyethylene glycol, glycerin, propylene glycol or other synthetic solvent; antimicrobial agents (such as benzyl alcohol and methyl parabens, phenols or cresols, mercurials, chlorobutanol, methyl and propyl p-hydroxybenzoic acid esters, thimerosal, benzalkonium chloride and benzethonium chloride); antioxidants (such as ascorbic acid and sodium bisulfite; methionine, sodium thiosulfate, platinum, catalase, citric acid,P-639811-PC cysteine, thioglycerol, thioglycolic acid, thiosorbitol, butylated hydroxyanisol, butylated hydroxytoluene, and / or propyl gallate) and chelating agents (such as ethylenediaminetetraacetic acid (EDTA)); buffers (such as acetates, citrates and phosphates). If administered intravenously, suitable pharmaceutically acceptable carriers include physiological saline or phosphate buffered saline (PBS), and solutions containing thickening and solubilizing agents, such as glucose, polyethylene glycol, polypropylene glycol and mixtures thereof.[000201] For any preparation used in the methods disclosed herein, the therapeutically effective amount or dose can be estimated initially from in vitro assays. For example, a dose can be formulated in animal models and such information can be used to more accurately determine useful doses in humans.[000202] Toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in humans . The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition.[000203] Depending on the severity and responsiveness of the condition to be treated, dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks or until cure is effected or diminution of the disease state is achieved. The amount of a composition to be administered will, of course, be dependent on e.g. the subject being treated, the severity of the affliction, the manner of administration, the judgment of the prescribing physician, etc.Methods of use[000204] According to the methods of the present disclosure, mRNA vaccines and compositions described herein are used for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.P-639811-PC[000205] In some embodiments, disclosed herein is a method of inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, the method comprising administering to the subject the vaccine disclosed herein, thereby inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in the subject.[000206] In some embodiments, disclosed herein is a method of inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, the method comprising administering to the subject the LNP disclosed herein, thereby inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in the subject.[000207] As used herein "allergy desensitization to peanuts" or "desensitization to peanuts", also termed "allergy immunotherapy", "allergy immunomodulation", or "allergen-specific immunotherapy", is a treatment aiming to reduce the severity of clinical reaction to peanuts and / or to increase the tolerated dose of peanuts and / or the longterm tolerance to peanuts. Peanut immunotherapy can be tested using methods known in the art, including a food challenge. Peanut immunotherapy may be partial, wherein the subject tolerates an increased amount of the food allergen compared to prior to treatment, but still reacts to higher doses of the food allergen; or the desensitization may be complete, wherein the patient tolerates all tested doses of the food allergen. In some embodiments, desensitization to peanuts comprises a reduced activation potential of basophils and / or mast cells compared to prior to treatment.[000208] As used herein "allergy immunomodulation" also termed "allergy desensitization", "allergy immunotherapy", or "allergen-specific immunotherapy", is a treatment aiming to reduce the severity of clinical reaction to peanuts, or to increase the tolerated dose of peanuts. Peanut immunotherapy can be tested using methods known in the art, including a food challenge. Peanut immunotherapy may be partial, wherein the subject tolerates an increased amount of the food allergen compared to prior to treatment, but still reacts to higher doses of the food allergen; or the desensitization may be complete, wherein the patient tolerates all tested doses of the food allergen.P-639811-PC[000209] As used herein, the terms "administering", "administer", or "administration" refer to the delivery of the compositions described herein to a subject, either parenterally, enterally, or topically. Illustrative examples of parenteral administration include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion. Illustrative examples of enteral administration include, but are not limited to, sublingual, and oral administration.[000210] In one embodiment, the vaccine or composition in the above methods is administered orally. In one embodiment, the vaccine or composition in the above methods is administered subcutaneously. In one embodiment, the vaccine or composition in the above methods is administered intramuscularly. In another embodiment, the vaccine or composition is administered by a route selected from subcutaneous, intramuscular, intravenous, intranasal, sublingual, topical, rectal or inhalation. In some embodiments, the administration is intramuscular, intravenous, subcutaneous, or intradermal administration. In some embodiments, the administration is intramuscular administration.[000211] In one embodiment, the subject in the above methods is an infant.[000212] In some embodiments, the subject, before administration, has one or more of the following: a positive SPT (skin prick test) to whole peanut (>5 mm) greater than control; peanut-specific IgE >5 kUA / L, and a dose-limiting symptom in DBPCFC <100 mg peanut protein.[000213] In some embodiments, the vaccine or composition according to the invention are administered in a therapeutically effective amount. The terms "effective", "efficacy," or "effectiveness" are used herein to refer to the ability of a therapy to induce immune-modulation or sustain a desired immune state, such as an immune-modulated state, unless otherwise indicated. As used herein, the term "effective amount" of a vaccine or composition is an amount sufficient to obtain beneficial or desired results, for example, clinical results, and, as such, an "effective amount" depends upon the contextP-639811-PC in which it is being applied. For example, in the context of administering a vaccine or composition that treats allergy, an effective amount of a composition is, for example, an amount sufficient to achieve treatment, as defined herein, as compared to the response obtained without administration of the composition. In some embodiments, a therapeutically effective amount is an amount of a vaccine or composition to be delivered (e.g., nucleic acid, drug, therapeutic composition) that is sufficient, when administered to a subject suffering from or susceptible to an allergy condition, to treat, improve or ameliorate symptoms of, prevent, and / or delay the onset of the allergy condition.[000214] In some embodiments, the terms "treat", "treating", and "treatment" are used synonymously herein to refer to any action providing a benefit to a subject afflicted with a disease state or condition, including improvement in the condition through lessening, inhibition, suppression, or elimination of at least one symptom; delay in progression of the disease; delay in recurrence of the disease; inhibition of the disease; or partially or fully reducing a response or reaction to an allergen.[000215] In some embodiments, the methods of the present disclosure comprise administering the LNP described herein or the composition described herein. In some embodiments, the LNP comprises at least one mRNA molecule encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof. In some embodiments, the LNP comprises a first mRNA molecule encoding de-epitoped Ara h 1 and a second mRNA molecule encoding de-epitoped Ara h 2.[000216] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleotide sequence set forth in SEQ ID NO: 2, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises the nucleotide sequence set forth in SEQ ID NO: 2, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 2.P-639811-PC[000217] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 4, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 4, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 4.[000218] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 16, or a fragment or variant thereof. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleotide sequence set forth in SEQ ID NO: 16, or a sequence having at least 85%, preferably at least 90%, more preferably at least 95%, such as 96%, 97%, 98% or 99%, identity to said sequence. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises a nucleic acid sequence with at least 80% identity to a nucleic acid sequence set forth in SEQ ID NO: 16.[000219] In some embodiments, de-epitoped Ara h 1 comprises an amino acid sequence set forth in SEQ ID NO: 1. In some embodiments, the de-epitoped Ara h 1 comprises the amino acid sequence set forth in SEQ ID NO: 1, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 1. In some embodiments, the de-epitoped Ara h 1 comprises an amino acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 1.[000220] In some embodiments, de-epitoped Ara h 2 comprises an amino acid sequence set forth in SEQ ID NO: 3. In some embodiments, the de-epitoped Ara h 2 comprises the amino acid sequence set forth in SEQ ID NO: 3, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 3. In some embodiments, the de-epitoped Ara h 2 comprises an amino acid sequence that isP-639811-PC at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 3.[000221] In some embodiments, de-epitoped Ara h 2 comprises an amino acid sequence set forth in SEQ ID NO: 21. In some embodiments, the de-epitoped Ara h 2 comprises the amino acid sequence set forth in SEQ ID NO: 21, or comprises an amino acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 21. In some embodiments, the de-epitoped Ara h 2 comprises an amino acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to an amino acid sequence set forth in SEQ ID NO: 21.[000222] In some embodiments, the mRNA molecule comprises at least one 5' untranslated region (5' UTR), at least one 3' untranslated region (3' UTR), and at least one polyadenylation (poly(A)) sequence. In some embodiments, the mRNA molecule further comprises a sequence encoding at least one signal sequence.[000223] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises a nucleic acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 18 or 20. In some embodiments, the mRNA molecule encoding de-epitoped Ara h 2 comprises the nucleic acid sequence set forth in SEQ ID NO: 18, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 18. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 2 comprises the nucleic acid sequence set forth in SEQ ID NO: 20, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 20.[000224] In some embodiments, the mRNA molecule encoding de-epitoped Ara h 1 comprises a nucleic acid sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to SEQ ID NO: 17 or 19. In some embodiments, the mRNA molecule encodingP-639811-PC de-epitoped Ara h 1 comprises the nucleic acid sequence set forth in SEQ ID NO: 17, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 17. In some embodiments, the mRNA molecule encoding de- epitoped Ara h 1 comprises the nucleic acid sequence set forth in SEQ ID NO: 19, or comprises an nucleic acid sequence having at least 80% identity with the amino acid sequence of SEQ ID NO: 19.[000225] Methods of diagnosing peanut allergy are known in the art and include immunological assays (such as peanut-specific IgE), skin prick tests, food challenges, and trial elimination diets. For diagnosis of peanut allergy by food challenge, the subject receives increasing doses of peanut protein. An observed allergic reaction to the peanut protein during the food challenge indicates the subject has a peanut allergy and is a candidate for variant protein immunotherapy. The judgment of whether a subject reacts to a particular dose during the food challenge depends on the test criteria, which can vary. A reaction in a food challenge can be judged by the severity of symptoms (e.g., mild, moderate, or severe) and / or the observability of the symptom (e.g., whether a symptom is subjectively reported by the patient or objectively observed by the medical caregiver). In some embodiments, the reaction is an anaphylactic reaction. In some embodiments, treatment with the variants disclosed herein results in a decreased anaphylactic reaction, e.g., from severe to a moderate reaction.[000226] The level of peanut specific IgE can be measured from a patient serum sample (i.e., to measure a serum level) or from a patient plasma sample (i.e., to measure a plasma level). Whole blood can be drawn from the patient, and the serum or plasma can be isolated from the whole blood using known methods. The level of ps-lgE can be measured in vitro, for example, using a quantitative immunoassay. Quantitative immunoassays are known in the art, and can include, but are not limited to, an enzyme- linked immunosorbent assay (ELISA); an alkaline phosphatase immunoassay autoanalyzer, such as an IMMULITE® system (Siemens Healthcare Diagnostics, Erlangen, Germany); a radioallergosorbent test (RAST), or a fluoroenzyme immunoassay autoanalyzer, such as the ImmunoCAP® system (Thermo Fisher Scientific / Phadia, Uppsala,P-639811-PCSweden) or UniCAP™ (Phadia AB, Uppsala, Sweden). A fluorescence enzyme immunoassay (FEIA) auto-analyzer (e.g., ImmunoCAP® system) is a preferred technique, although other techniques may be reliably used. For example, another technique may be used as the level of antibody (e.g., IgE) determined by that technique may be normalized to a measurement by a fluorescence enzyme immunoassay auto-analyzer. That is, a level of antibody (e.g., IgE) can be determined by a technique, and can correspond to a level as measured by a fluorescence enzyme immunoassay auto-analyzer. According to some embodiments, BAT or MAT assays may be used.[000227] The phrase "anaphylaxis" or "anaphylactic reaction", as used herein, refers to a subset of allergic reactions characterized by mast cell degranulation secondary to cross-linking of the high-affinity IgE receptor on mast cells and basophils induced by an anaphylactic allergen with subsequent mediator release and the production of severe systemic pathological responses in target organs, e.g., airway, skin digestive tract, and cardiovascular system. As is known in the art, the severity of an anaphylactic reaction may be monitored, for example, by assaying cutaneous reactions, puffiness around the eyes and mouth, vomiting, and / or diarrhea, followed by respiratory reactions such as wheezing and labored respiration. The most severe anaphylactic reactions can result in loss of consciousness and / or death.[000228] The phrase "decreased anaphylactic reaction", as used herein, relates to a decrease in clinical symptoms following treatment of symptoms associated with exposure to an anaphylactic allergen, which can involve exposure via cutaneous, respiratory, gastrointestinal, and mucosal (e.g., ocular, nasal, and aural) surfaces.[000229] The phrase "decreased anaphylactic reaction", as used herein, relates to a decrease in clinical symptoms following treatment of symptoms associated with exposure to an anaphylactic allergen, which can involve exposure via cutaneous, respiratory, gastrointestinal, and mucosal (e.g., ocular, nasal, and aural) surfaces.[000230] As used herein, a "subject" or "patient" (used interchangeably) refers in one embodiment, to a human or any other animal. In some embodiments, the subject is a human.P-639811-PC[000231] Dosages may be titrated to optimize safety and efficacy. Typically, dosageeffect relationships from in vitro studies can provide useful guidance on the proper doses for patient administration. Studies in animal models can also be used for guidance regarding effective dosages for immunization in accordance with the present disclosure. [000232] In some embodiments, more than one administration of vaccines described herein can be delivered to the subject in a course of immunization. Dependent upon the particular course of immunization, multiple administrations may be given to a subject, with the administration repeated at various time intervals.[000233] In some embodiments, the present disclosure provides a composition for use in inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, the composition comprising an mRNA of the present disclosure.[000234] In some embodiments, the present disclosure provides a vaccine for use in inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, the vaccine comprising an mRNA of the present disclosure. [000235] In some embodiments, the present disclosure provides a LNP for use in inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, the LNP comprising an mRNA of the present disclosure.[000236] In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, are administered to the subject at a dosage of between 10 ug / kg and 400 ug / kg of the mRNA. In some embodiments the dosage of the mRNA is 1-5 ug, 5- 10 ug, 10-15 ug, 15-20 ug, 10-25 ug, 20-25 ug, 20-50 ug, 30-50 ug, 40-50 ug, 40-60 ug, 60- 80 ug, 60-100 ug, 50-100 ug, 80-120 ug, 40-120 ug, 40-150 ug, 50-150 ug, 50-200 ug, 80- 200 ug, 100-200 ug, 120-250 ug, 150-250 ug, 180-280 ug, 200-300 ug, 50-300 ug, 80-300 ug, 100-300 ug, 40-300 ug, 50-350 ug, 100-350 ug, 200-350 ug, 300-350 ug, 320-400 ug, 40-380 ug, 40-100 ug, 100-400 ug, 200-400 ug, or 300-400 ug, 400-500 ug, 300-500 ug, 400-600 ug, 600-700 ug, 800-900 ug, 900-1000 ug per dose.P-639811-PC[000237] In some embodiments the dosage of the mRNA is 30 ug, 40 ug, 50 ug, 60 ug, 70 ug, 80 ug, 90 ug, 100 ug, per dose. In some embodiments the dosage of the mRNA is 30 ug per dose. In some embodiments the dosage of the mRNA is 100 ug, per dose.[000238] In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject by intradermal or intramuscular injection.[000239] In some embodiments, a dosage of 30 micrograms of the mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is included in the vaccine, composition or LNP administered to the subject. In some embodiments, a dosage of 100 micrograms of the mRNA molecules encoding de-epitoped Ara h 1, de- epitoped Ara h 2, or a combination thereof, is included in the vaccine, composition or LNP administered to the subject. In some embodiments, a dosage of 50 micrograms of the mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is included in the vaccine, composition or LNP administered to the subject. In some embodiments, a dosage of 75 micrograms of the mRNA molecules encoding de- epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is included in the vaccine, composition or LNP administered to the subject. In some embodiments, a dosage of 150 micrograms of the mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is included in the vaccine, composition or LNP administered to the subject. In some embodiments, a dosage of 400 micrograms of the mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is included in the vaccine, composition or LNP administered to the subject. In some embodiments, a dosage of 200 micrograms of the mRNA molecules encoding de- epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is included in the vaccine, composition or LNP administered to the subject.[000240] In some embodiments, the w:w ratio between the mRNA encoding de- epitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 is in a range ofP-639811-PC about 100:1 to about 1:1, or about 50:1 to about 1:1, or about 20:1 to about 1:1, or about 10:1 to about 1:1.[000241] In some embodiments, the w:w ratio between the mRNA encoding deepitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 is in a range of about 1:1 to about 1:100, or about 1:1 to about 1:50, or about 1:1 to about 1:20, or about 1:1 to about 1:10. In some embodiments, the ratio between the mRNA encoding de- epitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 is between about 100:1 to 1: 100 (w:w). In some embodiments, the ratio between the mRNA encoding de- epitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 is 1:1 (w:w).[000242] In some embodiments, the dosage may be delivered using multiple administrations (e.g., two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, or more administrations). In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject at least twice. In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject at least three times.[000243] In some embodiments, the number of doses administered to the subject is between 3 to 100. In some embodiments, the number of doses administered to the subject is at least 2. In some embodiments, the number of doses administered to the subject is at least 3. In some embodiments, the number of doses administered to the subject is between 2 to 200. In some embodiments, the number of doses administered to the subject is at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10.[000244] In some embodiments, the vaccine, composition or LNP described herein is administered to the subject three times a day, two times a day, once a day, every other day, every third day, every week, every two weeks, every three weeks, or every four weeks. In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combinationP-639811-PC thereof, is administered to the subject every 1 to 24 weeks. In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding deepitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject every 4 to 12 weeks. In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject every 6 to 10 weeks. In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject every 8 to 14 weeks. In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject every 1 to 36 weeks. In some embodiments, the vaccine, composition or LNP comprising one or more mRNA molecules encoding de-epitoped Ara h 1, de-epitoped Ara h 2, or a combination thereof, is administered to the subject every 1 to 56 weeks.[000245] In some embodiments, disclosed herein is a method of reducing a chronic risk of anaphylaxis in a patient suffering from a peanut allergy, comprising administering intramuscularly to the patient a 30 microgram or 100 microgram dose of a mRNA encoding a modified peanut protein selected the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, or a mixture thereof, every 4 or 12 weeks.[000246] In some embodiments, the 30 microgram or 100 microgram dose is a mixture of SEQ ID NO: 17 and SEQ ID NO: 18. In some embodiments, the 30 microgram or 100 microgram dose is a 1:1 (w:w) mixture of SEQ ID NO: 17 and SEQ ID NO: 18.[000247] In some embodiments, the total number of doses administered to the patient is 3, 4 or 5.[000248] In some embodiments, the patient has a decreased response to ingestion of peanuts after administration as measured by a DBPCFC procedure, as compared to a patient not administered the mRNA encoding modified peanut protein.[000249] In some embodiments, the dose comprises lipid nanoparticles encapsulating the mRNA.P-639811-PC[000250] In some embodiments, the patient, before administration, has one or more of the following: a positive SPT to whole peanut (>5 mm) greater than control; peanut-specific IgE >5 kUA / L, and a dose-limiting symptom in DBPCFC <100 mg peanut protein.[000251] In some embodiments, disclosed herein is a method of reducing an allergic reaction to peanuts in a subject, the method comprising administering a 30 microgram or 100 microgram dose of a 1:1 (w:w) mixture of SEQ ID NO: 17 and SEQ ID NO. 18 wherein the method comprises reducing the severity of the peanut allergic reaction in the subject or reducing the incidence of allergic reaction in the subject to peanuts.[000252] In some embodiments, the subject has food allergy to one or more food allergens selected from the group consisting of peanut, milk, egg, wheat, cashew, hazelnut, and walnut protein.[000253] In some embodiments, the subject is less than 6 years of age. In some embodiments, the subject is 1 year of age or older.[000254] In some embodiments, the subject has asthma. In some embodiments, the subject does not have asthma. In some embodiments, the method does not comprise concurrent oral immunotherapy.[000255] Unless specifically stated otherwise herein, references made in the singular may also include the plural. For example, "a" and "an" may refer to either one, or one or more.[000256] As used herein, the term "administering" refers to bringing in contact with a compound of the present disclosure. In some embodiments, the compositions are applied locally. In some embodiments, the compositions are applied systemically. Administration can be accomplished to cells or tissue cultures, or to living organisms, for example humans.[000257] As used herein, the terms "administering," "administer," or "administration" refer to deliver one or more compounds or compositions to a subjectP-639811-PC parenterally, enterally, or topically. Illustrative examples of parenteral administration include, but are not limited to, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular , subcapsular, subarachnoid, intraspinal and intrasternal injection and infusion. Illustrative examples of enteral administration include, but are not limited to inhalation, intranasal, sublingual, and rectal administration. Illustrative examples of topical administration include, but are not limited to, transdermal and vaginal administration. In particular embodiments, an agent or composition is administered parenterally, optionally by intravenous administration to a subject.[000258] In some embodiments, a composition of the present disclosure comprises a pharmaceutically acceptable composition. In some embodiments, the phrase "pharmaceutically acceptable" is employed herein to refer to those compounds, materials, compositions, combinations, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio.[000259] It is to be understood that the compositions and methods of the present disclosure comprising the elements or steps as described herein may, in some embodiments, consist of those elements or steps, or in some embodiments, consist essentially of those elements or steps. In some embodiments, the term "comprise" refers to the inclusion of the indicated active agents, as well as inclusion of other active agents, and pharmaceutically or physiologically acceptable carriers, excipients, emollients, stabilizers, etc., as are known in the pharmaceutical industry. In some embodiments, the term "consisting essentially of" refers to a composition, whose only active ingredients are the indicated active ingredients. However, other compounds may be included which are for stabilizing, preserving, etc. the formulation, but are not involved directly in the therapeutic effect of the indicated active ingredients. In some embodiments, the term "consisting essentially of" may refer to components which facilitate the release of theP-639811-PC active ingredient. In some embodiments, the term "consisting" refers to a composition, which contains the active ingredients and a pharmaceutically acceptable carrier or excipient.[000260] A skilled artisan would appreciate that the term "about", may encompass a deviance of between 0.0001-5% from the indicated number or range of numbers. Further, it may encompass a deviance of between 1 -10% from the indicated number or range of numbers. In addition, it may encompass a deviance of up to 25% from the indicated number or range of numbers.[000261] Throughout this disclosure, various embodiments may 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 on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub ranges 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 sub ranges 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, 3, 4, 5, and 6. This applies regardless of the breadth of the range.[000262] Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases "ranging / ranges between" a first indicated number and a second indicated number and "ranging / ranges from" a first indicated number "to" a second indicated number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals there between.[000263] It should be understood that the disclosure presented herein is not limited to the particular methodologies, protocols and reagents, and examples described herein. The terminology and examples used herein is for the purpose of describing particular embodiments only, for the intent and purpose of providing guidance to the skilled artisan, and is not intended to limit the scope of the disclosure presented herein.P-639811-PC[000264] The following examples are presented in order to more fully illustrate the preferred embodiments of the present disclosure. They should in no way be construed, however, as limiting the broad scope of the disclosure.EXAMPLESExample 1 - Materials and Methods[000265] Murine allergy immunotherapeutic potential study (utilized in Example 2}[000266] C3H / HeJ 5-7 week-old female mice were purchased from Jackson Laboratories (Strain #000659) and housed in specific pathogen-free conditions, room temperature 22°C with 12 hour light / dark cycle (N = 35). Lab Diet 5LOD chow food (peanut free, soy free diet) and filtered tap water provided ad libitum.[000267] Treatment Dosing Regimen: Naive mice were treated with the different mRNA molecules by 2 IM doses of 2 pg three weeks apart (days 1 and 22) and then boosted with a third IM dose of 20 pg approximately 3.5 weeks later on day 47 (see experimental scheme in Figure 2). mRNA-LNP formulations were administered intramuscularly. See Table 2 below.[000268] Naive mice (N=35) were used for determining the immunogenic potential of the various mRNA molecules. The immunogenic potential was determined by evaluating B-cell response by measuring the levels of IgGs produced against the combined modified allergens encoded by the mRNA molecules. IgG levels were determined by ELISA. IgGl and lgG2a antibody titers specific for DE-Ara h 1 and DE-Ara h 2 were assessed from sera one week after the second dose (day 29), 3 weeks after the second dose (day 43, only for DE-Ara h 2) and 2 weeks after the third dose (day 61) by ELISA. From 5 weeks (day 82) following the last dose, antibody titers specific for DE-Ara h 1 and DE-Ara h 2 were assessed every 3-4 weeks only for the groups treated with the selected candidates. The use of naive mice at this stage was crucial for evaluating the immunogenic potential since mice with a naive background have no memory response against peanut proteins.P-639811-PC[000269] Murine allergy model intramuscular (IM) immunotherapy efficacy study (utilized in Example 3)[000270] C3H / HeJ 4-5 week-old female mice were purchased from Jackson Laboratories (Strain #000659) and housed in specific pathogen-free conditions, room temperature 22°C with 12 hour light / dark cycle. Lab Diet 5LOD chow food (peanut free, soy free diet) and filtered tap water provided by the animal facility ad libitum.[000271] Sensitization: Mice were sensitized 8 times (weeks 0-5) with 2 mg peanut extract (prepared in house from 12% fat light roast peanut flour, Byrd Mill) + 10 pg cholera toxin (CTx) (List Biological Laboratories) diluted in PBS (HyClone Cytiva) to a total volume of 200 pl / per mouse administered by oral gavage after ~3 hours of fasting on Days 0,1,2, 7, 14, 21, 28 and 35. Blood was collected from the saphenous vein after the last sensitization and serum was separated by centrifugation. Peanut sensitization was verified by determining peanut-specific IgE titers in ELISA analysis following standard protocol for detection with alkaline-phosphatase-conjugated antibodies. Mice with titers below pre-defined cutoff value (sum of average absorbance + 2x the standard deviation in sera from naive mice) were removed from study, and remaining mice were assigned to groups according to titers to ensure each group has similar average IgE.[000272] Intramuscular (IM) immunotherapy: starting on day 49 mice received 1 injection every 3 weeks, a total of 3 intramuscular injections of PBS (negative controls) or mRNA, on days 49, 70 and 92. A sham mRNA (e.g. Ova mRNA) as an additional negative control, as well as a positive control group of subcutaneous immunotherapy with aqueous whole peanut protein extract (Stallergenes Greer) were included in the study (as described in Table 4). Mice were monitored once per hour for 4 hours and twice per hour from 4-6 hrs and then hourly for 7-8 hrs for anaphylaxis symptoms after each dose. Symptoms were scored on the 0-5 point scoring scale.[000273] Oral peanut challenge: starting on day 98, mice were fasted for 5-6 hours and then challenged by oral gavage (IG) with 25 mg peanut protein extract (prepared in house) in 200 pl volume, on days 98, 100, 102, 105, 107, 109, 112. Challenges were repeated on alternating days over a 2-week period and outcomes were reported for theP-639811-PC7th which typically results in the most severe reactions. Core body temperature was rectally monitored prior to challenge and at 15 minute intervals for at least 90 minutes, and severity of anaphylactic symptoms were scored using the common index (0, no symptoms; 1, prolonged rubbing and scratching around the nose, eyes or head; 2, puffiness around the eyes or mouth, piloerection, and / or decreased activity with increased respiratory rate; 3, labored respiration, wheezing, stridor, and / or cyanosis around the mouth and tail; 4, tremor, convulsion, no activity after prodding and / or moribund; 5, death).[000274] Serum mCPTl: Approximately 45-60 minutes after challenge, blood was collected by saphenous phlebotomy and serum was separated by centrifugation. Mast cell protease-1 (MCPT-1) release into serum was analyzed using a mouse MCPT-1 ELISA kit (Invitrogen).[000275] Cytokine release assay: Mice were euthanized by isoflurane overdose (VetOne). Spleen and mesenteric lymph nodes (mLN) were dissected, manually disrupted and filtered through 70um cell strainers (Fisher Scientific) to generate single-cell suspensions. Cells were depleted of red blood cells ACK lysing buffer (Gibco) and resuspended in cell culture media: DMEM (HyClone), 5% FBS (Gemini), 2mM L-glutamine (HyClone), ImM sodium pyruvate (Sigma), 10 mM MOPS (Sigma), 50 uM 2- mercaptoethanol (Gibco), 100 IU penicillin + 100 pg / ml streptomycin (Gibco). Cells were plated at 8xl05per well in 200 pl in flat bottom 96 well plates and incubated (37°C, 5% CO2) for 72 hours with either media alone (unstimulated), 200 pg / ml PE (Stallergenes), 100 pg / ml Ara h 1 or 100 pg / ml Ara h 2. Cell culture supernatants were analyzed for concentration of IL-4, IL-5 and IL-13 by Luminex multiplex analysis following manufacturer's instructions (Millipore- Milliplex). Data was presented as ([cytokine] from stimulated cells) - ([cytokine] from non-stimulated cells).[000276] The following ELISA test was utilized for both tested Studies.[000277] ELISA: Antigen-specific IgE, IgGl and lgG2a titers were determined and compared by an established ELISA assay. Maxisorp 96-well plates (Thermofisher scientific) were coated overnight at 4°C with lOOpI of protein at 2pg / ml in PBS. All subsequent stepsP-639811-PC were carried out at RT with PBST washes (PBS+0.05% Tween 20) between steps. Titration curves were created for each serum or plasma sample by diluting xlO and then serially x2.1 (for IgE detection) or x25 and then serially x2.5 (for IgG). Plates were blocked with PBST+2% BSA (Sigma) for 2 hours, incubated with titrated samples or without (blanks) for 2 hours, and then incubated with 1:5,000 HRP-Anti-mouse IgE or 1:20,000 HRP-Anti- mouse IgG for 1 hour. Finally, plates were incubated with lOOpI 1-Step Ultra TMB (Thermofisher) until color developed and lOOpI H2SO4 0.5M was added to stop the reaction. Optical density at 450nm was recorded using the Synergy LX microplate spectrophotometer (Biotek, Vermont), OD of blank wells (without sample), subtracted and area under curve calculated.[000278] Table 1: Sequences of mRNA moleculesP-639811-PCP-639811-PCP-639811-PCP-639811-PCP-639811-PCP-639811-PCP-639811-PCP-639811-PC[000279] The experiments below were carried out to examine the immunotherapeutic potential and efficacy in protection from a peanut allergen challenge of an mRNA molecule according to an embodiment of the invention.[000280] The immunotherapeutic potential was determined by evaluating the B-cell response measured as induction of IgG antibodies against the encoded proteins: DE-Ara h 1 and DE-Ara h 2 (SEQ ID NOs: 1 and 3, respectively).[000281] The efficacy of the mRNA molecule according to an embodiment of the invention was examined by in-vivo protection from peanut protein challenge in peanut sensitized mice, measured as: (1) reduction in anaphylactic symptoms score (scored on a 0-5 point scoring scale), (2) prevention of hypothermic reaction (measured as core body temperature drop) and (3) inhibition of mast cell protease-1 (MCPT-1) secretion. In addition, the beneficial effect of an mRNA molecule was examined in-vitro by measuring the T-cell cytokine response following stimulation of splenocytes and MLN cells with peanut proteins (whole peanut extract, Ara h 1 and Ara h 2). The secretion levels of I FNy, IL-4, IL-5, IL-10, and IL-13 were assessed by Luminex multiplex analysis following manufacturer's instructions (Millipore- Milliplex).Example 2 - Allergy immunotherapeutic potential of various mRNA molecules and various LNP formulations[000282] Aim-, identify an mRNA molecule which advantageously induces a relatively high B-cell response measured as an indication of IgG antibodies generated against the encoded proteins- DE-Ara h 1 and DE-Ara h 2. For this purpose, naive mice were treated as elaborated above under Murine allergy immunotherapeutic potential study.[000283] A combination of two separate mRNA molecules was used (see Table 1): the first molecule encodes a DE Ara h 1 (SEQ ID NO: 1); and the second molecule encodes a DE Ara h 2 protein (SEQ ID NO: 3). The two mRNA molecules were co-encapsulated in an LNP particle comprising ALC-0315™ (Acuitas Therapeutics) ([(4- hydroxybutyl)azanediyl]di(hexane-6,l-diyl) bis(2-hexyldeca noate)), ALC-0159 (Methoxypolyethyleneglycoloxy(2000)-N,N-ditetradecylacetamide), cholesterol, andP-639811-PCDSPC (l,2-distearoyl-sn-glycero-3-phosphocholine) in the molar ratio 47.5 : 1.8 : 40.7 : 10. Different LNP formulations, e.g., PBS with 10% Sucrose, were tested on their effect on the allergy immunotherapeutic potential. The two mRNA molecules were used in a 1:1 weight ratio.[000284] Each mRNA molecule was composed of (i) a 5'-cap structure; (ii) a 5' UTR; (iii) a signal peptide; (iv) an open reading frame (ORF) encoding the variant polypeptide and consisting of nucleotides including Nl-methyl-pseudouridine modifications (100% of the uridine nucleotide were replaced with Nl-methyl-pseudouridine); (v) a 3' UTR; and (vi) a poly-A region. The 5' UTR comprised a 'flank sequence', e.g., added for efficient in vitro transcription (IVT) of template DNA to mRNA.[000285] The signal peptide used in all mRNA molecules was the osteonectin signal peptide [Homo sapiens]; GenBank: AAA60993.1 (AA SEQ ID NO: 5). The signal peptide nucleic acid used in the molecule encoding was either SEQ ID NO: 6 or SEQ ID NO: 7.[000286] The 5' UTR, 3' UTR sequences as combined in the tested molecules were as elaborated in Table 2 below.[000287] Table 2: Immunotherapeutic potential Study DesignP-639811-PC* ALC-0315 (formulation 1) and ALC-0315 (formulation 2) have a storage temperature of -20°C, and - 80°C, respectively.[000288] Observations and Measures: Animal health checks were carried out at least once daily, blood collection was carried out; 100 pl, on days 0, 29, 43, 61, 82, then every 3-4 weeks only for the groups treated with the selected candidates, the serum was purified throughout the study according to the details specified in Table 3 below. The collected sera were stored at -80°C and evaluated at the end of the study for mouse IgG ELISA analysis.[000289] Animals were euthanized by isoflurane overdose, to effect, followed by thoracotomy. A maximum obtainable volume of whole blood was collected via cardiac stick and processed into a maximum obtainable volume of serum (spun at 10,000g for 10 minutes at room temperature). The serum was stored in 2 separate aliquots at nominally -70°C until analysis. Sample collection procedure is specified in Table 4 below.[000290] Table 3: Interim Sample Collection[000291] Outcome Measures: A successful immunotherapeutic composition was considered a composition that induces a relatively high IgG response against the proteins encoded by the molecule, DE-Ara h 1 and DE-Ara h 2, measured by antigen-specific IgG ELISA. These antibodies had the potential to bind the natural allergens, thus, reduced ability to induce allergic reactions.[000292] Results:P-639811-PC[000293] IgGl and lgG2a antibody titers against DE-Ara h 1 and DE-Ara h 2 were assessed by ELISA on days 29-61, for selecting the best formulation (Table 2). IM administration of different DE-Ara h 1+DE-Ara h 2 mRNA formulations to naive mice induced an anti-DE-Ara h 2 IgGl response (Figure 3A), an anti-DE-Ara h 2 lgG2a response (Figure 3B), anti-DE-Ara h 1 IgGl response (Figure 3C), and an anti-DE-Ara h 1 lgG2a response (Figure 3D). Generally, anti-DE-Ara h 2 titers were lower compared to anti-DE- Ara h 1 titers. The formulation of group E (ALC-0315 (formulation 2) with mRNA encoding DE Ara h 1 HBB-DE Arahl-HBB (SEQ ID NO: 17) and mRNA encoding DE Ara h 2 HBB-DE Arah2-HBB (SEQ ID NO: 18) elicited the most rapid response to DE-Ara h 2 and was unique in achieving in 100% of mice, a positive IgG response to DE-Ara h 2. Furthermore, this formulation yielded the highest mean DE-Ara h 2 antibody titers for both IgGl and lgG2a. [000294] The antibody kinetics of group E (ALC-0315 (formulation 2) with mRNA encoding DE Ara h 1 HBB-DE Arahl-HBB (SEQ ID NO: 17) and mRNA encoding DE Ara h 2 HBB-DE Arah2-HBB (SEQ ID NO: 18)) was monitored on days 29-208. IM administration of different DE-Ara h 1+DE-Ara h 2 mRNAs to naive mice induced robust and durable anti- DE-Ara h 1 and anti-DE-Ara h 2 IgGl responses (Figure 3E) and robust and durable anti- DE-Ara h 1 and anti-DE-Ara h 2 lgG2a responses (Figure 3F).Example 3 - Allergy immunotherapeutic efficacy of mRNA molecules[000295] Aim-, evaluate the immunotherapeutic efficacy of mRNA molecules using a peanut allergy mouse model. For this purpose, Murine allergy model intramuscular (IM) immunotherapy efficacy study is carried out.[000296] Experimental design: peanut sensitized mice are treated with the mRNA molecules by 3 i.m. injections and efficacy is evaluated by (1) reduction in anaphylactic symptoms score (2) preventions of hypothermic reaction (measured as core body temperature drop), (3) inhibition of mast cell protease-1 (MCPT-1) secretion and (4) T-cell cytokine response following stimulation with peanut proteins. See study design in Table 4 and schematic timeline in Figure 1.P-639811-PC[000297] Sensitization Phase: Groups are dosed with sensitization solution (PBS with 2 mg peanut extract +10 pg cholera toxin) on Days 0,1,2, 7, 14, 21, 28 and 35. Unsensitized sham treatment group, is given a gavage of PBS with 2 mg peanut extract, excluding cholera toxin.[000298] Mice are bled after the final sensitization, on day 39, and sera is analyzed for peanut specific IgE. Mice are distributed based upon the level of peanut-specific IgE into groups (shown in Table 4), to ensure that all mice that proceed in the study are sufficiently sensitized and groups have similar antibody titers.[000299] Treatment: On Day 49, 70 and 92, mice are dosed with 40 pl Treatment solution (See Table 4 below). All dosing is performed via injection. Anaphylaxis symptoms are evaluated after each dose. Symptoms are scored on the 0-5 point scoring scale.[000300] The mRNA composition used is as elaborated in Example 2.[000301] Challenge Phase: Mice are challenged 7 times by an oral gavage (i.g.) of 20 mg in-house prepared peanut extract (days 98, 100, 102, 105, 107, 109, 112). Symptoms and temperatures are monitored at the final (7th) oral challenge.[000302] Table 4: Allergy immunotherapeutic efficacy study DesignP-639811-PC[000303] Observations and Measures: Animal health checks are carried out at least once daily as a cage-side health check. Clinical observations are performed for all animals on Day 1 prior to Sensitization and once weekly thereafter including prior to euthanasia. Clinical observations are performed more often if abnormal clinical signs are exhibited by animals in the study.[000304] Anaphylaxis Scoring: clinical scoring is performed on all animals following the 7th oral peanut challenge. The following scoring system is used:0: No clinical symptoms1: Itching around the mouth, nose and / or eyes2: Edema / puffiness around eyes and / or mouth, Decreased activity, hunched / scruffy 3: Periods of motionless for > 1 min, lying prone. Labored breathing, wheeze / stridor 4: No responses to whisker stimuli, reduced or no response to prodding5: T remor, convulsion, or death[000305] Body Weights: Body weights are recorded following sensitization, beginning on Day 48, prior to administration of the test material and once a week thereafter, including prior to euthanasia. Body weights are rounded to the nearest 0.1g.[000306] Core Body temperature: Core body temperature (measurement via a rectal probe) are recorded on Day 98 before oral challenge and on 15, 30, 45, 60, 75, and 90 minutes (±10% deviation) after challenge, or until body temperatures have returned to at least 36°C.[000307] Measurement of mast cell protease-1. Mice are bled at approximately 60 minutes following the 7th challenge for mast cell protease-1 (MCPT-1) quantification. Approximately 30 pl of whole blood is collected. In the event that a mouse has a bodyP-639811-PC temperature lower than 36°C, bleeding occurs once the body temperature returns to at least 36°C. Concentration of MCPT-1 in the serum is measured by the O'Konek lab by ELISA.[000308] Interim Blood Collection: ~100uL of whole blood is collected from each animal via the saphenous vein following the last sensitization (Day 39) and one day prior to each i.m. immunotherapy dose , on Days 48, 69 and 91. Blood samples are processed into a maximum obtainable volume serum (spun at 10,000g for 10 minutes at room temperature). Samples are stored at nominally -70°C until analysis at the completion of the study.[000309] Terminal Procedures[000310] Euthanasia and Blood and Tissue Collection: Mice are sacrificed 3 days after the final challenge (Day 115). All the animals are euthanized by isoflurane overdose, to effect, followed by thoracotomy, and the following tissues are collected for analyses: [000311] A maximum obtainable volume of whole blood is collected via terminal cardiac puncture and processed into a maximum obtainable volume of serum (spun at 10,000g for 10 minutes at room temperature).[000312] Spleens and mesenteric lymph nodes (mLN) are harvested. Single cell suspensions are prepared and plated at 800,000 cells per well in flat bottom 96 well plates and stimulated in duplicate with the following: a) media (unstimulated control) b) peanut extract (200 pg / ml) c) Natural Ara h 2 (100 pg / ml) d) Natural Ara h 1 (100 pg / ml)[000313] Splenocytes are stimulated with all 3 conditions. Cell number may be limiting for lymph node cultures. In the event that there are not enough cells from lymph nodes, priority are given to unstimulated and PE stimulation conditions, with Ara h 2 and Ara h 1 stimulations performed if there are sufficient cells.[000314] Cell culture supernatants are harvested after 72 hours. Cytokines (IFNy, IL- 4, IL-5, IL-10, IL-13) are measured by Luminex multiplex assay in selected samples.P-639811-PC[000315] Outcome Measures: A successful immunotherapeutic composition is considered a composition that (1) reduces anaphylactic symptoms (2) prevents hypothermic reaction (3) inhibits mast cell protease-1 (MCPT-1) secretion; and (4) skews the T-cell cytokine response following stimulation with peanut proteins away from Th2; all as compared to sensitized mice treated with PBS (sensitized sham).Example 4 -Human Protocols[000316] A Phase l / 2a, first-in-human, open-label, multicenter study is conducted in adult participants (ages 18-55, inclusive) with peanut allergy in four sequential cohorts evaluating two dose levels and two dose intervals.[000317] The study is designed to evaluate the safety and efficacy of repeated administration (3 doses) of a 1:1 (w:w) mixture of mRNA encoding two modified peanut proteins, DE-Ara h 1 and DE-Ara h 2 (SEQ ID NO: 17 and SEQ ID NO: 18). These modified peanut proteins are recombinant engineered versions of the two major natural peanut allergens Ara h 1 and Ara h 2 proteins, respectively, each with reduced ability to bind human allergen-specific immunoglobulin E (IgE) antibodies in the serum of peanut allergic individuals. Participants are administered in either low dose (30 pg) or high dose (100 pg) at Q4W or Q12W. The exploration of both 4 and 12 weeks between doses is to evaluate whether longer time between doses permits additional maturation of high affinity IgG from germinal center B cells capable of binding to peanut allergens with potential to sterically hinder binding of peanut antigens to participant's IgE.[000318] The study is comprised of a screening period, treatment period, and follow-up period. Throughout the study, participants are evaluated every 4 weeks or every 12 weeks.[000319] Participants are assigned sequentially to one of the four treatment cohorts, A, B, C or D, as shown in Table 5. Cohorts A and C are dosed every 4 weeks (Q4W), on Day 1, Week 4 and week 8. In Cohorts B and D participants are dosed every 12 weeks (Q12W) on Day 1, Week 12 and Week 24.[000320] Table 5: Treatment Cohorts by Dose RegimenP-639811-PCAbbreviations: IM, intramuscular; Q4W, every 4 weeks; Q12W, every 12 weeks; TBD, to be determined.[000321] Assessments:[000322] Assessments include Double Blind placebo controlled food challenge(DBPCFC). The DBPCFC is performed by feeding gradually increasing amounts of a suspect allergenic food (in this case, peanuts, presented as defatted peanut flour) mixed in a vehicle (matrix) food under physician observation. For this study, a uniform approach to food challenge, in accordance with the PRACTALL consensus guidelines for DBPCFC, is used at all investigational sites. According to the PRACTALL guidelines, the challenge doses start at 1-3 mg and increase in semi-log increments to a maximum dose of 3000 mg. DBPCFC is performed for initial (Screening) for eligibility and at 4 and 6 weeks after last dose of study drug.[000323] Assessments also include Skin Prick Test (SPT) for peanuts. The standard SPT is performed on the volar surface of the patient's forearm using standardized, commercially available whole peanut extract), 1:10 w / v and is performed at screening and EOS. A positive result is >5 mm determined over control, baseline reactivity by averaging maximal perpendicular wheal diameters 15 minutes after applying the lancet. The positive control is histamine base, 6 mg / mL and with a wheal >3 mm indicating a valid test. The negative control is glycerol saline. The titrated SPT is the skin testing for atopic response at different concentrations of peanut extract with saline as negative control and histamine as positive controls.P-639811-PC[000324] Safety assessments include: adverse events, safety laboratories, spirometry / pulmonary function test to participants with asthma, physical examinations, vital signs and electrocardiogram at specified timepoints.[000325] Inclusion Criteria:[000326] To be eligible for participation in this study, participants must meet all the following:[000327] Age: Adult participants 18-55 years old, inclusive.[000328] Type of Participant and Disease Characteristics:1. Documented history of physician-diagnosed peanut allergy.2. A positive SPT to whole peanut (>5 mm) greater than control.3. Peanut-specific IgE >5 kUA / L.4. Dose-limiting symptom in DBPCFC<100 mg peanut protein.

Claims

P-639811-PCCLAIMS1. A mRNA molecule comprising:(i) at least one untranslated region (5' UTR) comprising SEQ ID NO: 15 or a fragment or variant thereof;(ii) an ORF encoding de-epitoped Ara h 1 comprising the nucleic acid sequence of SEQ ID NO: 2 or a fragment or variant thereof; and(iii) at least one untranslated region (3' UTR) comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

2. The mRNA molecule of claim 1, wherein the 5' UTR comprises the nucleic acid sequence of SEQ ID NO: 8.

3. The mRNA molecule of claim 1 or 2, wherein the mRNA molecule further comprises a sequence segment encoding at least one signal sequence.

4. The mRNA molecule of claim 3, wherein the signal sequence comprises a nucleic acid sequence encoding SEQ ID NO: 5.

5. The mRNA molecule of claim 3 or 4, wherein the signal sequence comprises the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7.

6. The mRNA molecule of any one of claims 1-5, comprising the elements:(i) a 5' UTR comprising the nucleic acid sequence of SEQ ID NO: 15;(ii) a signal sequence comprising the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7;(iii) an ORF encoding de-epitoped Ara h 1 having the nucleic acid sequence of SEQ ID NO: 2;(iv) a 3' UTR having the nucleic acid sequence of SEQ ID NO: 9 or SEQ ID NO: 10; and(v) a poly(A) tail.

7. The mRNA molecule of any one of claims 1-6, comprising the elements:(i) a 5' UTR having the nucleic acid sequence of SEQ ID NO: 8;(ii) a signal sequence comprising the nucleic acid sequence of SEQ ID NO: 6 or SEQ ID NO: 7;P-639811-PC(iii) an ORF encoding de-epitoped Ara h 1 having the nucleic acid sequence of SEQ ID NO: 2;(iv) a 3' UTR having the nucleic acid sequence of SEQ ID NO: 10; and(v) a poly(A) tail.

8. A mRNA molecule comprising:(i) at least one 5' UTR comprising SEQ ID NO: 15 or a fragment or variant thereof;(ii) an ORF encoding de-epitoped Ara h 2 comprising the nucleic acid sequence ofSEQ ID NO: 4 or SEQ ID NO: 16, or a fragment or variant thereof; and(iii) at least one 3' UTR comprising SEQ ID NO: 9 or SEQ ID NO: 10, or a fragment or variant thereof.

9. The mRNA molecule of claim 8, comprising the elements:(i) at least one 5' UTR comprising SEQ ID NO: 8 or a fragment or variant thereof;(ii) an ORF encoding de-epitoped Ara h 2 comprising the nucleic acid sequence ofSEQ ID NO: 16, or a fragment or variant thereof;(iii) at least one 3' UTR comprising SEQ ID NO: 10, or a fragment or variant thereof; and(iv) a poly(A) tail.

10. A mRNA molecule comprising a sequence selected from SEQ ID NOs: 17 and 19.

11. A mRNA molecule comprising a sequence selected from SEQ ID NOs: 18 and 20.

12. A mRNA molecule comprising a sequence having at least 90%, 95%, 97% or 99% similarity to sequence selected from the group consisting of SEQ ID NOs: 17, 18, 19 and 20.

13. The mRNA molecule of any one of claims 1-12, wherein the mRNA comprises one or more modified nucleotides.

14. The mRNA molecule of claim 13, wherein at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the uracil nucleotides in the mRNA are modified.P-639811-PC15. The mRNA molecule of claim 13, wherein at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or 100% of the uracil nucleotides in the ORF are modified.

16. The mRNA molecule of any one of claims 13-15 wherein the modification is selected from the group consisting of pseudouridine, Nl-methylpseudouridine, 2- thiouridine, 4'-thiouridine, 5-methylcytosine, 2-thio-l-methyl-l-deaza- pseudouridine, 2-thio-l-methyl-pseudouridine, 2-thio-5- aza-uridine, 2-thio- dihydropseudouridine, 2-thio-dihydrouridine, 2-thio-pseudouridine, 4-methoxy- 2- thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-l-methyl-pseudouridine, 4- thio- pseudouridine, 5-aza-uridine, dihydropseudouridine, 5-methyluridine, 5- methyluridine, 5- methoxyuridine, and 2'-O-methyl uridine.

17. The mRNA molecule of claim 16, wherein the modification is Nl- methylpseudouridine.

18. A pharmaceutically acceptable composition comprising a de-epitoped Ara h 1 mRNA molecule of any one of claims 1-7 or 10 and a de-epitoped Ara h 2 mRNA molecule of any one of claims 8-9 or 11.

19. The pharmaceutically acceptable composition of claim 12, where the de-epitoped Ara h 1 mRNA molecule and the de-epitoped Ara h 2 mRNA molecule are present in a ratio of about 10:0.1 to about 0.1:10 (w / w).

20. The composition of any one of claims 18-19, wherein the ratio between the mRNA encoding de-epitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 is about 1:1 (w:w).

21. A lipid nanoparticle encapsulating the a) de-epitoped Ara h 1 mRNA selected from SEQ ID NO 17 or 19, and b) a de-epitoped Ara h 2 mRNA selected from SEQ ID NO 18 and 20.

22. The lipid nanoparticle of claim 21, wherein the weight ratio of the de-epitoped Ara h 1 and the mRNA molecule encoding de-epitoped Ara h 2 in the lipid nanoparticle is about 1:1 (w:w).P-639811-PC23. The lipid nanoparticle of claim 21 or 22, wherein the lipid nanoparticle comprises[(4-hydroxybutyl)azanediyl]di(hexane-6,l-diyl) bis(2-hexyldeca noate),(Methoxypolyethyleneglycoloxy(2000)-N,N-ditetradecylacetamide), cholesterol and l,2-distearoyl-sn-glycero-3-phosphocholine in the molar ratio 47.5 : 1.8 : 40.7 : 10.

24. A vaccine comprising the lipid nanoparticle of any one of claims 20-23.

25. The vaccine of claim 24, wherein the vaccine is formulated for intramuscular injection.

26. A pharmaceutical composition comprising the lipid nanoparticle of any one of claims 20-23 and a pharmaceutically acceptable excipient.

27. The pharmaceutical composition of claim 26, comprising about lpg to lmg of the mixture of the de-epitoped Ara h 1 mRNA and the de-epitoped Ara h 2 mRNA.

28. The pharmaceutical composition of claim 26 or 27, comprising about 30 pg or 100 pg of the mixture of the de-epitoped Ara h 1 mRNA and the de-epitoped Ara h 2 mRNA.

29. A method for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, said method comprising administering to said subject the mRNA any one of claims 1-17 thereby inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.

30. A method for inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts, said method comprising administering to said subject the vaccine of claims 24-25 or the pharmaceutical composition of claims 26-28, thereby inducing desensitization to peanuts and / or immunomodulation of a response to peanuts in a subject allergic to peanuts.

31. The method of claim 29 or 30 wherein the administration is intramuscular, intravenous, subcutaneous, or intradermal administration.

32. The method of claim 29 or 30 wherein the administration is intramuscular administration.P-639811-PC33. The method of any one of claims 29-32, wherein the number of doses administered to the subject is at least 3.

34. The method of any one of claims 29-32, wherein the total number of doses administered to the subject is at least 3.

35. The method of any one of claims 29-32, wherein said mRNA, composition or vaccine is administered every 1 to 24 weeks.

36. The method of any one of claims 29-32, wherein said mRNA, composition or vaccine is administered every 4 to 12 weeks.

37. The method of any one of claims 29-32, wherein the subject has a decreased response to ingestion of peanuts as measured by a DBPCFC procedure.

38. The method of any one of claims 29-32, wherein the subject, prior to administration, has one or more of the following: a positive SPT to whole peanut (>5 mm) greater than control; peanut-specific IgE >5 kUA / L, and a dose-limiting symptom in DBPCFC <100 mg peanut protein.

39. A method of reducing a chronic risk of anaphylaxis in a patient suffering from a peanut allergy, comprising administering intramuscularly to the patient a 30 microgram or 100 microgram dose of a mRNA encoding a modified peanut protein selected the group consisting of SEQ ID NO: 17, SEQ ID NO: 18, or a mixture thereof, every 4 or 12 weeks.

40. The method of claim 39, wherein the 30 microgram or 100 microgram dose is a mixture of SEQ ID NO: 17 and SEQ ID NO: 18.

41. The method of claim 39 or 40, wherein the 30 microgram or 100 microgram dose is a 1:1 (w:w) mixture of SEQ ID NO: 17 and SEQ ID NO: 18.

42. The method of claim 39, where the total number of doses administered to the patient is 3, 4 or 5.

43. The method of any one of claims 39-42 wherein the patient has a decreased response to ingestion of peanuts after administration as measured by a DBPCFC procedure, as compared to a patient not administered the mRNA encoding modified peanut protein.P-639811-PC44. The method of any one of claims 39-43 wherein the dose comprises lipid nanoparticles encapsulating the mRNA.

45. The method of any one of claims 39-43, wherein the patient, before administration, has one or more of the following: a positive SPT to whole peanut (>5 mm) greater than control; peanut-specific IgE >5 kUA / L, and a dose-limiting symptom in DBPCFC <100 mg peanut protein.

46. A method of reducing an allergic reaction to peanuts in a subject, the method comprising administering a 30 microgram or 100 microgram dose of a 1:1 (w:w) mixture of SEQ ID NO: 17 and SEQ ID NO. 18 wherein the method comprises reducing the severity of the peanut allergic reaction in the subject or reducing the incidence of allergic reaction in the subject to peanuts.

47. The method of claim 46, wherein the subject has food allergy to one or more food allergens selected from the group consisting of peanut, milk, egg, wheat, cashew, hazelnut, and walnut protein.

48. The method of claim 46 or 47, wherein the subject is less than 6 years of age.

49. The method of claim 48, wherein the subject is 1 year of age or older.

50. The method of any one of claims 46-49, wherein the subject has asthma.

51. The method of claims 46-49, wherein the subject does not have asthma.

52. The method of claim 46-49, wherein the method does not comprise concurrent oral immunotherapy.

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