WO2019112489A1

WO2019112489A1 - Methods and agents for treatment of aging and aging related conditions and diseases

Info

Publication number: WO2019112489A1
Application number: PCT/RU2018/050156
Authority: WO
Inventors: Petr Olegovich Fedichev; Alexandr Alexandrovich ZENIN; Yuriy Sergeevich AULCHENKO; Maksim Nikolaevich KHOLIN
Original assignee: Limited Liability Company "Gero"
Priority date: 2017-12-05
Filing date: 2018-12-05
Publication date: 2019-06-13

Abstract

A methods, agents and pharmaceutical compositions for treatment of aging, frailty and aging related conditions and diseases are provided.

Description

ME THODS AND AGENTS FOR TREATMENT OF AGING AND AGING

RELATED CONDI TIONS AND DISEASES

BACKGROUND

[1] Improved methods and apparatus for treatment of frailty, aging and other Aging related conditions and diseases would be beneficial for improving health management. However, prior approaches to treatment of Aging related conditions and diseases can be less than ideal in at least some respects. For example, prior approaches can be less than ideal and may provide less efficacy than would be ideal.

[2] In light of the above it would be desirable to have improved methods and agents for Aging related conditions and diseases .

SUMMARY

[ 3 ] The present disclosure provides improved methods and agents that may be used for treatment and prevention of aging related conditions and diseases.

[ 4 ] In one aspect, the genes associated with the single nucleotide polymorphisms (SNPs) rs76207570, rs3811444, rs6741951, rs 143761991, rs35801134, rs34651, rs2250127, rs6891621, rs9272588, rs 10947428, rs7808664, rsl3282106, rs55964818, rsl0793962, rs4332427 , rsl50080415, rsll852372, rs3743445, rs9892942, rs7502233, rs463312, rs62217799, rsl43728189 are aging related therapeutic targets, as well as the proteins encoded by such genes.

[ 5 ] In one aspect, list of genes to be silenced for therapeutic purposes (treatment and prophylaxis of aging, frailty and aging related conditions and diseases. MACF1, OXCT2P1, SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1

[6] The corresponding proteins MACF1, OXCT2P1, SLC12A7, CTC- 228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1 are therapeutic targets to be inhibited or degraded for therapeutic purposes (treatment and prophylaxis of aging, frailty and aging related conditions and diseases (ARCD) .

[7] In one aspect, any of the genes MACF1, OXCT2P1, SLC12A7, CTC-228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1 could be silenced by at least one of the tools known in the art, such as by the RNAi, CRISPR, or siRNA etc. The types of silencing that could be applied include, but not limit to Transcriptional (Genomic Imprinting, Paramutation, Transposon silencing (or Histone Modifications), Transgene silencing, Position effect, RNA-directed DNA methylation etc.), Post-transcriptional (RNA interference, RNA silencing, Nonsense mediated decay etc.), Meiotic ( Transvection, Meiotic silencing of unpaired DNA etc) .

[8] In one aspect, the list of genes which expression should be increased or which should be activated for therapeutic purposes (treatment and prophylaxis of aging, frailty and aging related conditions and diseases: PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1

The corresponding proteins PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3, TUBB1 are therapeutic targets to be activated or added for therapeutic purposes (treatment and prophylaxis of aging, frailty and ARCD)

[ 9 ] In one aspect, the activation of the protein could be achieved by any methods known in the art, by small molecules, peptides, aptamers, antibodies, proteins or any other agents or methods, activating any of the following proteins: PABPC4, TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1.

INCORPORATION BY REFERENCE

[ 10 ] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig 1 Overview of RNA interference (cited from Matzke MA et al . Planting the Seeds of a New Paradigm. PLOS Biology 2004, 2(5) : el33 ) .

Fig 2 General mechanism utilized by ribozymes to cleave RNA molecules (Web. 25.09.2017, https://en.wikipedia.org/wiki/Gene_silencing#/media/File : Ribozym e_mechanism.png, Wikipedia Foundation, Inc)

Fig 3 Basic mechanism used by viral vectors to deliver genes to target cells. Example shown is a lentiviral vector (Web. 25.09.2017, https://en.wikipedia.org/wiki/Viral_ vector#/media/File : Lentiviral_vector .png, Wikipedia Foundation, Inc) .

DETAILED DESCRIPTION

[11] While various embodiments of the disclosure have been shown and described herein, those skilled in the art will understand that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the disclosure. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed.

[ 12 ] The term "about" and its grammatical equivalents in relation to a reference numerical value can include a range of values up to plus or minus 10% from that value. For example, the amount "about 10" can include amounts from 9 to 11. The term "about" in relation to a reference numerical value can include a range of values plus or minus 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% from that value.

[ 13 ] The term "at least" and its grammatical equivalents in relation to a reference numerical value can include the reference numerical value and greater than that value. For example, the amount "at least 10" can include the value 10 and any numerical value above 10, such as 11, 100, and 1,000.

[ 14 ] The term "at most" and its grammatical equivalents in relation to a reference numerical value can include the reference numerical value and less than that value. For example, the amount "at most 10" can include the value 10 and any numerical value under 10, such as 9, 8, 5, 1, 0.5, and 0.1.

[ 15 ] As used herein the singular forms "a", "an", and "the" can include plural referents unless the context clearly dictates otherwise. All technical and scientific terms used herein can have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs unless clearly indicated otherwise.

[ 16 ] The term "subject," as used herein, generally refers to an animal, such as a mammalian species (e.g., human) or avian (e.g., bird) species, or other organism, such as a plant. More specifically, the subject can be a vertebrate, e.g., a mammal such as a mouse, a primate, a simian or a human. Animals include, but are not limited to, farm animals, sport animals, and pets. A subject can be a healthy individual, an individual that has or is suspected of having a disease or a pre-disposition to the disease, or an individual that is in need of therapy or suspected of needing therapy. A subject can be any individual human being.

[ 17 ] The term "polynucleotide," as used herein, generally refers to a molecule comprising one or more nucleic acid subunits. A polynucleotide can include one or more subunits selected from adenosine (A) , cytosine (C) , guanine (G) , thymine (T) and uracil (U) , or variants thereof. A nucleotide can include A, C, G, T or U, or variants thereof. A nucleotide (nt) can include any subunit that can be incorporated into a growing nucleic acid strand. Such subunit can be an A, C, G, T, or U, or any other subunit that is specific to one or more complementary A, C, G, T or U, or complementary to a purine (i.e., A or G, or variant thereof) or a pyrimidine (i.e., C, T or U, or variant thereof) . A subunit can enable individual nucleic acid bases or groups of bases (e.g., AA, TA, AT, GC, CG, CT, TC, GT, TG, AC, CA, or uracil-counterparts thereof) to be resolved. In some examples, a polynucleotide is deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) , or variants or derivatives thereof. A polynucleotide can be single-stranded or double-stranded.

[ 18 ] The term "genome" generally refers to an entirety of an organism's hereditary information. A genome can be encoded either in DNA or in RNA. A genome can comprise coding regions that code for proteins as well as non-coding regions. A genome can include the sequence of all chromosomes together in an organism. For example, the human genome has a total of 46 chromosomes. The sequence of all of these together constitutes a human genome.

[ 19 ] The term "genetic variant," as used herein, generally refers to an alteration, variant or polymorphism in a nucleic acid sample or genome of a subject. Such alteration, variant or polymorphism can be with respect to a reference genome, which may be a reference genome of the subject or other individual. Single nucleotide polymorphisms (SNPs) are a form of polymorphisms. In some examples, one or more polymorphisms comprise one or more single nucleotide variations (SNVs), insertions, deletions, repeats, small insertions, small deletions, small repeats, structural variant junctions, variable length tandem repeats, and/or flanking sequences. Copy number variants (CNVs), transversions and other rearrangements are also forms of genetic variation. A genomic alternation may be a base change, insertion, deletion, repeat, copy number variation, transversion, or a combination thereof.

[20] The terms "frailty" and "longevity" are used interchangeably throughout this specification, and refer to a measure of one or more of an expected life span, genetic predisposition to premature death, rate of death, and frailty risk relative to average group. The terms "longevity associated genes" and "frailty associated genes" are used interchangeably throughout this specification and refer to genes with desired correlation with frailty or longevity.

[ 21 ] Aging related conditions and diseases (ARCD) -any diseases or conditions associated with aging, including but not limited to atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension, neurodegenration, and Alzheimer's disease, Dementia, Stroke, Atrophic gastritis, osteoarthritis, NASH, Camptocormia, Chronic obstructive pulmonary disease, Coronary artery disease, Dopamine dysregulation syndrome, metabolic syndrome, Effort incontinence, Hashimoto's thyroiditis, Heart failure , late life depression, Myocardial infarction, acute coronary syndrome,

Parkinson's disease, Sarcopenia, Sarcopenic obesity, Senile osteoporosis, Urinary incontinence etc. Aging related change in any parameters of organism is also regarded an ARCD as an aging related condition, including but not limited to aging related change in blood parameters, heart rate, cognitive functions/decline, bone density, Basal Metabolic Rate, Systolic blood pressure, Heel bone mineral density (BMD) , Heel quantitative ultrasound index (QUI), Heel broadband ultrasound attenuation, Heel broadband ultrasound attenuation, Forced expiratory volume in 1-second (FEV1), Forced vital capacity (FVC), Peak expiratory flow (PEF) , Duration to first press of snap-button in each round, Mean time to correctly identify matches, Hand grip strength (right and left) , Whole body fat-free mass, Leg fat-free mass (right and left) , time for recovery after the stress (wound, operation, chemotherapy, disease, change in lifestyle etc.) etc. Rejuvenating effect, increase in healthspan and lifespan are also regarded as treatment and prophylaxis of ARCD.

[22] As used herein, the term "nucleic acid" refers to genetic material (e.g., oligonucleotides or polynucleotides comprising DNA or RNA) . In some embodiments, the nucleic acid of the compositions is RNA. Suitable RNAincludes mRNA, siRNA, miRNA, snRNA and snoRNA. Contemplated nucleic acids also include large intergenic non coding RNA (lincRNA), which generally do not encode proteins, but rather function, for example, in immune signaling, stem cell biology and the development of disease. (See, e.g., Guttman, et al . , 458: 223-227 (2009); and Ng, et al . , Nature Genetics 42: 1035- 1036 (2010), the contents of which are incorporated herein by reference) . The nucleic acids of the invention include, but not limit to RNA or stabilized RNA encoding a protein or enzyme. The present invention contemplates the use of such nucleic acids (and in particular RNA or stabilized RNA) as a therapeutic capable of facilitating the expression of a functional enzyme or protein. The term "functional", as used herein to qualify a protein or enzyme, means that the protein or enzyme has biological activity, or alternatively is able to perform the same, or a similar function as the native or normally-functioning protein or enzyme. The subject nucleic acid compositions of the present invention are useful for the treatment of aging, frailty and ARCD

[23] RNA interference (RNAi) is a natural process used by cells to regulate gene expression. The process to silence genes first begins with the entrance of a double-stranded RNA (dsRNA) molecule into the cell, which triggers the RNAi pathway. The double-stranded molecule is then cut into small double-stranded fragments by an enzyme called Dicer. These small fragments, which include small interfering RNAs (siRNA) and microRNA (miRNA) , are approximately 21-23 nucleotides in length. The fragments integrate into a multi-subunit protein called the RNA-induced silencing complex, which contains Argonaute proteins that are essential components of the RNAi pathway. One strand of the molecule, called the "guide" strand, binds to RISC, while the other strand, known as the "passenger" strand is degraded. The guide or antisense strand of the fragment that remains bound to RISC directs the sequence-specific silencing of the target mRNA molecule. The genes can be silenced by siRNA molecules that cause the endonucleatic cleavage of the target mRNA molecules or by miRNA molecules that suppress translation of the mRNA molecule. With the cleavage or translational repression of the mRNA molecules, the genes that form them are essentially inactive. RNAi is thought to have evolved as a cellular defense mechanism against invaders, such as RNA viruses, or to combat the proliferation of transposons within a cell's DNA. Both RNA viruses and transposons can exist as double- stranded RNA and lead to the activation of RNAi. Currently, siRNAs are being widely used to suppress specific gene expression and to assess the function of genes. Companies utilizing this approach include Alnylam, Sanofi, Arrowhead, Discerna and Persomics, among others (Web. 25.09.2017 https://en.wikipedia.org/wiki/Gene_silencing, Wikipedia Foundation, Inc) .

[24] siRNAs can now be easily produced by the methods known in the art and modified to be used invivo . Another option could be a purchase of siRNAs or siRNAs modified for invivo use for respective targets. For example Ambion® In Vivo siRNAs are designed using the Silencer® Select algorithm and incorporate chemical modifications that help provide superior serum stability for in vivo delivery.

[25] Invitrogen™ Silencer™ Pre-designed siRNAs are available for all human, mouse, and rat gene targets in the RefSeq database. These siRNAs are designed for maximum potency and specificity using a highly effective and extensively tested algorithm. Each siRNA is synthesized to the highest quality standards and is provided with full sequence information. Furthermore, when one purchases three Silencer Pre-Designed siRNAs to the same target, there is a guarantee that with at least two of the siRNAs you will achieve >70% reduction in target mRNA levels.

[26] The further modification and optimisation of siRNAs for human use is made by the methods known in the art.

Antisense therapy is a form of treatment. When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid (DNA, RNA or a chemical analogue) that will bind to the messenger RNA (mRNA) produced by that gene and inactivate it, effectively turning that gene "off". This is because mRNA has to be single stranded for it to be translated. Alternatively, the strand might be targeted to bind a splicing site on pre-mRNA and modify the exon content of an mRNA. Delivery Because nucleases that cleave the phosphodiester linkage in DNA are expressed in almost every cell, unmodified DNA molecules are generally degraded before they reach their targets. Therefore, antisense drug candidate molecules are generally modified during the drug discovery phase of their development. Additionally, most targets of antisense are located inside cells, and getting nucleic acids across cell membranes is also difficult. Therefore, most clinical candidates have modified DNA "backbones", or the nucleobase or sugar moieties of the nucleotides are altered. Additionally, other molecules may be conjugated to antisense molecules in order to improve their ability to target certain cells or to cross barriers like cell membranes or the blood brain barrier. (Web. 25.09.2017 https://en.wikipedia.org/wiki/Antisense_therapy, Wikipedia Foundation, Inc) .

Some aspects of the present invention relate to at least one of the following items:

1. Method of treatment of at least one selected from the group: aging, frailty or aging related conditions and diseases (ARCD) comprising reduction or inhibition of protein selected from the group MACF1 , 0XCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1 , MAN2A2 , ERAL1, DHRS13, TUBB1 in patient by therapeutic mean.

2. Method of item 1 comprising administering an inhibitor of protein selected from the group MACF1, 0XCT2P1, SLC12A7, CTC- 228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1 or pharmaceutical composition, comprising an inhibitor of such protein .

3. Method of item 1, comprising administering an agent to reduce expression of a gene product encoded from at least one gene selected from the group MACF1 , 0XCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1 , MAN2A2 , ERAL1, DHRS13, TUBB1.

4. Method of item 3, wherein agent is siRNA, shRNA or other

RNA.

5. Pharmaceutical composition, comprising an inhibitor of protein selected from the group MACF1, 0XCT2P1, SLC12A7, CTC- 228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1.

6. Pharmaceutical composition of item 4, wherein inhibitor is a small molecule, peptide, aptamer, protein, antibody or agent for protein degradation. 7. Pharmaceutical composition, comprising an agent to reduce expression of a gene product encoded from a gene encoding protein selected from the group MACF1, OXCT2P1, SLC12A7, CTC- 228N24.3, PSMA4, RCCD1, MAN2A2 , ERAL1 , DHRS13, TUBB1.

8. Pharmaceutical composition of item 7, wherein agent is a gene therapy.

9. Pharmaceutical composition of item 7, wherein agent is siRNA, shRNA or other RNA.

10. Pharmaceutical composition, comprising an inhibitor of protein selected from the group MACF1, OXCT2P1, SLC12A7, CTC- 228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1 for the treatment of aging, frailty or ARCD.

11. A pharmaceutical composition comprising a gene therapy vector encoding gene selected from the group MACF1, OXCT2P1, SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1 and a pharmaceutically acceptable excipient.

12. Method of treatment of at least one selected from the group: aging, frailty or aging related conditions and diseases (ARCD) comprising increasing expression or activation of protein selected from the group PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3, TUBB1 in patient by therapeutic mean.

13. Method of item 1 comprising administering an activator of protein selected from the group PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3, TUBB1 or pharmaceutical composition, comprising an activator of such protein.

14. Method of item 1, comprising administering an agent to increase expression of a gene product encoded from at least one gene selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1.

15. Pharmaceutical composition, comprising an activator of protein selected from the group PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3 , TUBB1.

16. Pharmaceutical composition of item 13, wherein activator is a small molecule, peptide, aptamer, antibody or protein .

17. Pharmaceutical composition, comprising an agent to increase expression of a gene product encoded from a gene encoding protein selected from the group PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3 , TUBB1.

18. Pharmaceutical composition of item 16, wherein agent is a gene therapy.

19. Pharmaceutical composition, comprising an activator of protein selected from the group PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3, TUBB1 for the treatment of aging, frailty or ARCD.

20. A pharmaceutical composition comprising a gene therapy vector encoding gene selected from the group PABPC4, TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1 and a pharmaceutically acceptable excipient.

21. Pharmaceutical composition, comprising protein selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1 for the treatment of aging, frailty or ARCD. EXAMPLES

Example 1

To achieve the therapeutic effect any of the genes MACF1, OXCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1 , DHRS13, TUBB in model animal can be targeted by siRNA. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, resulting in no translation.

RNAi (siRNA, shRNA) as well as non-viral DNA vectors can be delivered in vivo using a synthetic carrier for the siRNA or shRNA/DNA payload or naked DNA vectors or chemically modified siRNA (i.e. Ambion In Vivo siRNA) . Synthetic carriers include cationic liposomes (stable nucleic-acid lipid particle SNALP carrier by Tekmira, siRNA-lipoplex AtuPLEX™) , anionic liposome, polymeric carriers (cyclodextrin nanoparticles from Calando, biodegradable polymeric matrix LODER) . For example, for systemic delivery of Ambion In Vivo siRNA (a dose starting with 7 mg/kg should be used) injection of siRNA solution of 0.7 mg/mL in PBS, saline (0.9% NaCl or variants containing sugars such as mannitol or glucose (5-15%) or Ringer's solution (147 mM NaCl, 4 mM KC1, 1.13 mM CaCl2) may be used. For hepatic delivery Invivofectamine 2.0 reagent (Invitrogen) may be used (~3 mg/mL working solution) . In order to prepare Invivofectamine-siRNA complex resuspended siRNA duplex should be diluted 1:1 Complexation Buffer. Then the solution should be added to an equal volume of warm Invivofectamine 2.0 Reagent, vortex for 2-3 seconds and incubated for 30 minutes at 50°C. Afterwards ~14 volumes of PBS, pH 7.4 should be added. The solution is then diafiltrated using Amicon® Ultra-15 Centrifugal Device with Ultracel-50 membrane. The retentate retentate containing the Invivofectamine 2.0-siRNA complex is then collected, brought to 00 pL with PBS and used for in vivo injection immediately or alternatively can be stored at 4°C for up to a week prior to injection. Specific silencing of targeted genes can be confirmed by the independent experiments known in the art.

Example 2

Examples of RNA that can be used m therapeutic formulation to treat aging, frailty and ARCD for silencing for therapeutic purposes (treatment and prophylaxis of aging, frailty and aging related conditions and disease the following genes MACF1, OXCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1 , MAN2A2 , ERAL1 ,

DHRS13, TUBB1

MACF1

1. shRNA Description shRNA Sequences

shRNA 1 for MACF1 (NM_012090 ) AAACGTTCACCAAGTGGGTCAAC shRNA 2 for MACF1 (NM 012090) AAGAGCACACCCAGGAGGATTTA shRNA 3 for MACFl (NM_012090 ) AAATCAGCCAGATCAAGATATTA shRNA 4 for MACFl (NM_012090 ) AAAGACTGTGATGTACAGGGTTT

Ready-to-package AAV shRNA clones of microtubule-actin crosslinking factor 1 (MACFl), transcript variant 1 in pAV-U6-GFP vector, 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences for research use it is available at ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave, Rockville, MD 20850 USA. RefSeq# NM_012090 Cat# SH821927 Procedure of packaging is described at https : //www . vigenebio . com/ service/AAV/

All examples of shRNA constructs available from ViGene Biosciences Inc mentioned in this application are Ampicillin resistant. To prepare DNA from the glycerol stock, the bacterial stock should be streaked on petri dish, grow overnight, and single colonies should be picked for DNA prep and confirmation. The plasmids are ready for AAV viral particle packaging. Please visit AAV packaging service page for more details . https : / /www . vigenebio . com/ shRNA/human/SH833212/PSMA4-

AAV

2) Crispr-cas9

Kit Components

KN213124G1, MACFl gRNA vector 1 in pCas-Guide vector

KN213124G2, MACFl gRNA vector 2 in pCas-Guide vector

KN213124D, donor vector containing Left and right homologous arms and GFP-Puro functional cassette.

Available for research use at OriGene Technologies, Inc. 9620 Medical Center Dr., Suite 200, Rockville, MD

20850 http : / /www. origene . com/CRISPR-CAS9/KN213124/MACF1. knockout

3) siRNA

Identifier Type Guide

Sequence Passenger Sequence

MACFl-1 siRNA UCCAUCGAGCAUUGAUCUCTT GAGAUCAAUGCUCGAUGGATT MACF1-2 siRNA UAAUUGUGGUAUCAUACACTT GUGUAUGAUACCACAAUUATT MACF1-3 siRNA UCAAGUAGUUGAUUAUAAGTT CUUAUAAUCAACUACUUGATT

OXCT2P1

siRNAs are available at

1. catalogue # s34375 at Thermo Fisher Scientific Inc. https : //www . thermofisher . com/order/genome- database/details/ sirna/ s34375?pluginName=&CID=&ICID=

2 ) https : //www . novoprolabs . com/p/human-oxct2pl-sirna- oligo-933595. html

Name: Homo sapiens 3-oxoacid CoA-transferase 2 pseudogene 1 (OXCT2P1), non-coding RNA Length: 1804 bp, by the product items 933595-1, 933595-la, 933595-lb, 933595-lc

SLC12A7

shRNA

This list includes all shRNAs that have a perfect SDR match to Human XM 017008958.1, regardless of what transcript they were originally designed to target. For example, this list can include shRNAs that were originally designed to target: (i) a different isoform or obsolete version of this transcript (as annotated by NCBI), (ii) a transcript of an orthologous gene (in this collection, generally human-to-mouse or mouse-to-human) , or (iii) a transcript of a different gene (from the same or different taxon) . Taxon, "Gene ID", "Gene Symbol" , Transcript , "Clone

ID", "Legacy Clone Name" , "Target Seq" , Vector, "Match

Position" , "Match Region" , "Match %","SDR Match %"," Intrinsic Score" , "Adjusted Score" , "Matches Other Gene in Same Taxon? ", "Orig . Target Gene ID", "Orig. Target Gene Symbol Forward Oligo Sequence" , "Reverse Oligo Sequence"

human, 10723 , SLC12A7 , XM_017008958.1 , TRCN0000238384 , NM_006598

.2-

3667s21cl, CCCAGTGGTTAGGTTGCATTT , pLKO_TRC005 , 3986, 3UTR, 100, 100, 10 .8, 15.12, N, 10723, SLC12A7 , CCGGCCCAGTGGTTAGGTTGCATTTCTCGAGAAATGCAA CCTAACCACTGGGTTTTTG, AATTCAAAAACCCAGTGGTTAGGTTGCATTTCTCGAGAAATGCA ACCTAACCACTGGG human, 10723 , SLC12A7 , XM_017008958.1 , TRCN0000238385 , NM_006598

.2-

1438s21cl, GCCATAGTGACGACGTCTTTC, pLKO_TRC005 , 1742, CDS, 100, 100, 10. 8, 15.12, N, 10723, SLC12A7 , CCGGGCCATAGTGACGACGTCTTTCCTCGAGGAAAGACGT CGTCACTATGGCTTTTTG, AATTCAAAAAGCCATAGTGACGACGTCTTTCCTCGAGGAAAGACG TCGTCACTATGGC human, 10723 , SLC12A7 , XM_017008958.1 , TRCN0000238386 , NM_006598

.2-

614s21cl, GCGGGTCCTACTACATGATAT , pLKO_TRC005 , 918, CDS, 100, 100, 13.2,

9.24 , N, 10723, SLC12A7 , CCGGGCGGGTCCTACTACATGATATCTCGAGATATCATGTAGT AGGACCCGCTTTTTG, AATTCAAAAAGCGGGTCCTACTACATGATATCTCGAGATATCATGTAG TAGGACCCGC human, 10723 , SLC12A7 , XM_017008958.1 , TRCN0000238388 , NM_006598

.2-

863s21cl, TCTTCGTGGGCGTCAAGTATG, pLKO_TRC005 , 1167, CDS, 100,100,10.8 , 7.56, N, 10723, SLC12A7 , CCGGTCTTCGTGGGCGTCAAGTATGCTCGAGCATACTTGACG CCCACGAAGATTTTTG, AATTCAAAAATCTTCGTGGGCGTCAAGTATGCTCGAGCATACTTGAC GCCCACGAAGA human, 10723 , SLC12A7 , XM_017008958.1 , TRCN0000042968 , NM_006598

.1-

4537slcl, CCTCCCTTTCTATGTGGCATA, pLKO .1 , 4918, 3UTR, 100,100,4.05,2.8 35, N, 10723, SLC12A7 , CCGGCCTCCCTTTCTATGTGGCATACTCGAGTATGCCACATAGAA AGGGAGGTTTTTG, AATTCAAAAACCTCCCTTTCTATGTGGCATACTCGAGTATGCCACATAGA AAGGGAGG

human, 10723 , SLC12A7 , XM_017008958.1 , TRCN0000042970 , NM_006598

.1-

197 s lcl , GAAGGGAAGAACATGGCACTT , pLKO .1 , 563, 5UTR, 100, 100, 4.05, 2.835 , N, 10723, SLC12A7 , CCGGGAAGGGAAGAACATGGCACTTCTCGAGAAGTGCCATGTTCTTC CCTTCTTTTTG, AATTCAAAAAGAAGGGAAGAACATGGCACTTCTCGAGAAGTGCCATGTTCTT CCCTTC human, 10723 , SLC12A7 , XM_017008958.1 , TRCN0000238387 , NM_006598

.2-

3299s21cl, TGATCACCATCTACTCCTAAT , pLKO_TRC005 , 3618, CDS, 100,100,10. 8, 6.48, N, 10723, SLC12A7 , CCGGTGATCACCATCTACTCCTAATCTCGAGATTAGGAGTA GATGGTGATCATTTTTG, AATTCAAAAATGATCACCATCTACTCCTAATCTCGAGATTAGGAGT AGATGGTGATCA

Ready-to-package AAV shRNA clones of solute carrier family 12 (potassium/chloride transporters), member 7 (SLC12A7) in pAV-U6-

GFP vector, 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences

Gene Name: SLC12A7 ; DKFZp434F076; KCC4

cDNA size: 3252 bp Ready-to-package AAV shRNA clones spcifications

Product Description: 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences

Volume: 200 ul

Shipping Condition: Ambient

Storage Medium: LB with 25% glycerol with appropriate antibiotics

Storage Condition: -80 °C

Biosafety Level/Hazardous: BSL-1

Shelf Life: 10 years

Notes: All the shRNA constructs are Ampicillin resistant. To prepare DNA from the glycerol stock, the bacterial stock should be streaked on petri dish, grow overnight, and single colonies should be picked for DNA prep and confirmation. The plasmids are ready for AAV viral particle packaging.

Description shRNA Sequences

shRNA 1 for SLC12A7 (NM_006598) GGGAGATGGAAATCCAAGAGAAA shRNA 2 for SLC12A7 (NM_006598) TTTTTCTGACGTACATCTCCCCG shRNA 3 for SLC12A7 (NM_006598) GGCATCTACTTCCCTTCCGTGAC shRNA 4 for SLC12A7 (NM 006598) TTCATCTGCTCCTGGTACTACGC

For research use it is available at ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave Rockville, MD 20850 USA. siRNA

NMJ06598 SLC12A7 10421 ACGGATGCACAGAAGTCCATC

NMJ06598 SLC12A7 10422 ACCATACGGTCCCTAATGAGC

NMJ06598 SLC12A7 10423 ACGCTCAATGGCGTCGTCCTC

PSMA4

PSMA4 siRNAs can be acquired from many commercial sources, e . g .

1. http : //dharmacon . gelifesciences . com/ sirna/accell- sirna-reagents-human/ ?term=&productId=Al 0E5AC6-306C-4B71-BE03- 62ACA0C4D34D&sourceId=entrezgene/5685 catalogue number E-017211- 00-0005

2. catalogue numbers NM_001102667, NM_001102668,

NM_002789 , NM 017281, NM_011966 at Sigma-Aldrich Co. LLC . 3. catalogue numbers 903821-la, 903821-lb ,903821-lc,

903821-2a, 903821-2b, 903821-2c at https : //www . novoprolabs . com/p/human-psma4-sirna-oligo- 903821.html etc.

shRNA

Description shRNA Sequences

shRNA for PSMA4 (NM_001102668) AACTAAGGCTCATTGCTCAAAGG shRNA

for PSMA4 (NM_001102668) AAACAAGCTTATACACAATTTGG shRNA

for PSMA4 (NM_001102668) GGGATAAGCACTATGGCTTTCAG shRNA

for PSMA4 (NM_001102668) TTGGAAATAATAGCGCTGCAGCT

Ready-to-package AAV shRNA clones of proteasome (prosome, macropain) subunit, alpha type, 4 (PSMA4)) , ttranscriiptt variiantt 33 m pAV-U6-GFP vector, 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences RefSeq# NM_001102668 Cat# SH833212 cDNA size: 573 b are available for research use at

ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave,

Rockville, MD 20850 USA. Product Description: 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences.

RCCD1

shRNA

Description shRNA Sequences

shRNA for RCCD1 (NM_001017919) GGAGCTACACCGCTTTCGTGACC shRNA

for RCCD1 (NM_001017919) GGAGGCGTTACTGCAGGTCTGGG shRNA

for RCCD1 (NM_001017919) CCGAGCACGCGTTGCTGCTGGAC shRNA

for RCCD1 (NM 001017919) GGCCTAGTCATGGCTGAGGTGGC

Ready-to-package AAV shRNA clones of RCC1 domain containing 1 (RCCD1), transcript variant 2 in pAV-U6-GFP vector, 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences RefSeq# NM_001017919 Cat# SH838998 Gene Name: RCCD1; MGC14386 cDNA size: 1131 bp for research use is available at ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave,

Rockville, MD 20850 USA. siRNA

TACGTCCAAGGTCGGGCAGGAAGA

MAN2A2

shRNA

Description shRNA Sequences

shRNA 1 for MAN2A2 (NM_006122 ) TTCTCGCTCTACCTCATGCTGGA shRNA 2 for MAN2A2 (NM_006122 ) GGGCAGCTGGAGATTGCGACAGG shRNA 3 for MAN2A2 (NM_006122 ) CCCAGTTTGGCACTCTTTCTGAC shRNA 4 for MAN2A2 (NM 006122) CCGTGCAGATCAGCGCACACTGG

Ready-to-package AAV shRNA clones of mannosidase, alpha, class 2A, member 2 (MAN2A2) in pAV-U6-GFP vector, 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences RefSeq# NM_006122 Cat# SH825785 Gene Name: MAN2A2; MANA2X cDNA size: 3453 b for research use is available at ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave, Rockville, MD 20850 USA. siRNA

GGCUGGAGUGCAGUGGCAUTT GTCCGACCUCACGUCACCGUA

ERAL1

shRNA

Description shRNA Sequences

shRNA 1 for ERALl (NM_005702 AACAGAGATGAGCAGGATGTCCT shRNA 2 for ERALl (NM_005702 ; AAACAGAAGAGGCATCACCTGGA shRNA 3 for ERALl (NM_005702 ; AAGCAGAAGTCAGTTCTCCTGGA shRNA 4 for ERALl (NM 005702; AAACACTAAAGCAATACCTTCTG

Ready-to-package AAV shRNA clones of Era G-protein-like 1 (E. coli) (ERALl) in pAV-U6-GFP vector, 4 predesigned shRNA in pAV- U6-GFP vector + 1 negative control with scrambled sequences RefSeq# NM_005702 Cat# SH821072 Gene Name: ERALl; ERA; ERALIA; H-ERA; HERA-A; HERA-B cDNA size: 1314 bp for research use is available at ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave, Rockville, MD 20850 USA.

siRNA

GGAAGGUGCAUACUACUCGTT GTCCUUCCACGUAUGAUGAGC

DHRS13 shRNA

Description shRNA Sequences

shRNA 1 for DHRS13 (NM_144683 ) CCAGGAGAGTGGGAACAATGAGG shRNA 2 for DHRS13 (NM_144683 ) CCATATCGGTCCCTTTCTGCTGA shRNA 3 for DHRS13 (NM_144683 ) GGGAGCTCGCCAACCAGCTTGAG shRNA 4 for DHRS13 (NM 144683) TTGTGCTCTACAAGAGGGCATCG

Ready-to-package AAV shRNA clones of dehydrogenase/reductase (SDR family) member 13 (DHRS13) in pAV-U6-GFP vector, 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences RefSeq# NM_144683 Cat# SH817739

Gene Name: DHRsl3; MGC23280; SDR7C5 cDNA size: 1134 bp for research use are available at ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave, Rockville, MD 20850 USA.

siRNA

1. DHRS13 siRNA (h) catalogue number - sc-93828 at Santa Cruz Biotechnology, Inc https://www.scbt.com/scbt/product/dhrsl3- sirna-h-shrna-and- lentiviral-particle-gene- silencers

2. Catalogue No . : abx914098 at https : / /www. abbexa . com/products/ reagents-and-tools/dhrsl3-sirna 3. Catalogue No.: 932281-la, 932281-lb, 932281-lc https : / /www . novoprolabs . com/p/human-dhrsl3-sirna-oligo- 932281.html

4. Catalog No. ABIN3312580 at https : //www . genomics- online . com/gene-index-d/dhrsl3/

TUBB1

shRNA

Description shRNA Sequences

shRNA 1 for TUBB (NM_178014 ) CCAAGTTCTGGGAGGTGATCAGT shRNA 2 for TUBB (NM_178014 ) CCGAGCTGGTTGATTCTGTCCTG shRNA 3 for TUBB (NM_178014 ) GGTGCCTTCACCCAAAGTGTCTG shRNA 4 for TUBB (NM 178014) CCAGCTCAATGCTGACCTCCGCA

Ready-to-package AAV shRNA clones of tubulin, beta (TUBB) in pAV-U6-GFP vector, 4 predesigned shRNA in pAV-U6-GFP vector + 1 negative control with scrambled sequences

RefSeq# NM_178014 Cat# SH846423 Gene Name: TUBB; M40; MGC117247; MGC16435; OK/SW-cl.56; TUBB1 ; TUBB5 cDNA size: 1335 bp for research use are available at ViGene Biosciences Inc. Address: Suite 105, 9430 Key West Ave, Rockville, MD 20850 USA. siRNA

siRNA could be obtained

1. catalogue number - SR414740 at OriGene Technologies,

2. Accession NO.: NM_001080971.2 Name:Mus musculus tubulin, beta 1 class VI (Tubbl), mRNA Length:2004 bp Encoded protein :NP_001074440.1 954538-1, 954538-la, 954538-lb, 954538- lc at https : //www. novoprolabs . com/p/mouse-tubbl-sirna-oligo- 954538.html

3. Abbexa Ltd, Innovation Centre, Cambridge Science Park, Cambridge, CB4 0EU, UK

Telephone: +44 (0) 1223 755950 - Fax: +44 (0) 1223 755951 -

E-Mail: info@abbexa.com

Registered in England: 8475531 - VAT Reg No: GB 167 9240

79 TUBB1 siRNA, Catalogue No . : abx938558

4) Thermo Fisher Scientific Inc siRNA ID s37479 https : //www . thermofisher . com/order/genome- database/details/ sirna/ s37479

Example 3 siRNA Mediated Inhibition of Gene Expression

• In a six well tissue culture plate, seed 2 x 105 cells per well in 2 ml antibiotic-free normal growth medium supplemented with FBS .

NOTE: This protocol is recommended for a well from a 6 well tissue culture plate. Adjust cell and reagent amounts proportionately for wells or dishes of different sizes. • Incubate the cells at 37° C in a C02 incubator until the cells are 60-80% confluent. This will usually take 18-24 hours.

NOTE: Healthy and subconfluent cells are required for successful transfection experiments. It is recommended to ensure cell viability one day prior to transfection.

• Prepare the following solutions:

• Solution A: For each transfection, dilute 2-8 mΐ of siRNA duplex (i.e., 0.25-1 pg or 20-80 pmols siRNA) into 100 mΐ siRNA

Transfection Medium: sc-36868.

• Solution B: For each transfection, dilute 2-8 mΐ of siRNA Transfection Reagent: sc-29528 into 100 mΐ siRNA Transfection Medium: sc-36868. Peak activity should be at about 6 mΐ siRNA Transfection Reagent.

NOTE: Do not add serum and antibiotics to the siRNA

Transfection Medium: sc-36868

NOTE: Optimal siRNA amount used for transfection may vary for each target protein and should be determined experimentally.

NOTE: If a lower siRNA concentration is desired, dilute siRNA appropriately with siRNA Dilution Buffer: sc-29527.

NOTE: Although highly efficient in a variety of cell lines, siRNA Transfection Reagent: sc-29528 may not be suitable for use with all cell lines.

• Add the siRNA duplex solution (Solution A) directly to the dilute Transfection Reagent (Solution B) using a pipette. Mix gently by pipetting the solution up and down and incubate the mixture 15-45 minutes at room temperature.

• Wash the cells once with 2 ml of siRNA Transfection Medium: sc-36868 Aspirate the medium and proceed immediately to the next step.

• For each transfection, add 0.8 ml siRNA Transfection Medium to each tube containing the siRNA Transfection Reagent mixture (Solution A + Solution B) . Mix gently and overlay the mixture onto the washed cells

• Incubate the cells 5-7 hours at 37° C in a C02 incubator.

NOTE: Longer transfection times may be desirable depending on the cell line. However prolonged serum starvation may result in unwanted cell detachment or death.

NOTE: Fluorescein Conjugated Control siRNA should only be incubated for a total 5-7 hours at 37° C in a C02 incubator. At the end of incubation they are ready to be assayed by fluorescent microscopy .

• Add 1 ml of normal growth medium containing 2 times the normal serum and antibiotics concentration (2x normal growth medium) without removing the transfection mixture. If toxicity is a problem, remove the transfection mixture and replace with lx normal growth medium.

• Incubate the cells for an additional 18-24 hours.

• Aspirate the medium and replace with fresh lx normal growth medium.

• Assay the cells using the appropriate protocol 24-72 hours after the addition of fresh medium in the step above.

NOTE: Controls should always be included in siRNA experiments. Use either Control siRNAs: sc-37007, sc-44230, sc- 44231, sc-44232, sc-44233, sc-44234, sc-44235, sc-44236, sc-44237 or sc-44238 or Control siRNA (Fluorescein Conjugates) : sc-36869, sc-44239, sc-44240 or sc-44241. Each contain a scrambled sequence that will not lead to the specific degradation of any known cellular mRNA.

NOTE: For Western blot analysis prepare cell lysate as follows: Wash cells once with PBS. Lyse cells in 300 mΐ lx electrophoresis sample Buffer (sc-24945: Electrophoresis Sample Buffer, 2X) by gently rocking the 6 well plate or by pipetting up and down. Sonicate the lysate on ice if necessary.

NOTE: For RT-PCR analysis isolate RNA using the method described by Chomczynski and Sacchi (Anal Biochem. 1987 Apr; 162(1) : 156-159. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Chomczynski P, Sacchi N.) or a commercially available RNA isolation kit.

Catalogue numbers of reagents starting with sc- in this example are as described and available at Santa Cruz Biotechnology, Inc . https : / /www . scbt . com/ scbt/home

Example 4

Ex-vivo gene therapy in cultured cells (e.g. hematopoietic) which are then reintroduced to a patient by the methods known in the art is possible by different therapeutic gene constructs, delivered by viral and non-viral vectors or siRNA, or electroporation. For example, PBMC can be collected from the patients, washed with PBS and subjected to enzymatic treatment with DNase (Sigma, St. Louis, MO) for 1 hour at 37°C, and rested overnight in a 5% C02 incubator in X-VIVO culture medium (Lonza) . The next day cells should be diluted with fresh media supplemented with 1,000 Cetus units of rIL-2/ml to a concentration of 1.5 million cells per ml for 3 days for cell expansion.

For transduction PBMCs should be washed twice with culture medium and mixed with the lentiviral vector supernatant ( lmg vector per lx 10^s cells), protamine sulfate (Sigma) should be added at the final concentration of 6 mg/ml, and the transduction plates should be incubated overnight at 37°C, 5% C02. PBMCs should be washed twice with culture medium and seeded at a density of 10^s cells/ml in X-VIVO medium with 1,000 Cetus units of rIL-2/ml. Forty-eight hours later cells should be harvested and reintroduced to the patient.

Example 5

Agents for increasing gene expression.

PABPC4

Premade Adenovirus with ORF of poly (A) binding protein, cytoplasmic 4 (inducible form) (PABPC4), transcript variant 3 with C terminal Flag and His tag. ATGAACGCTGCGGCCAGCAGCTACCCCATGGCCTCCCTGTACGTGGGCGACCTGCATTC GGACGTCACCGAGGCCATGCTGTACGAAAAGTTCAGCCCCGCGGGGCCTGTGCTGTCCATCCGG GTCTGCCGCGATATGATCACCCGCCGCTCCCTGGGCTATGCCTACGTCAACTTCCAGCAGCCGG CCGACGCTGAGCGGGCTTTGGACACCATGAACTTTGATGTGATTAAGGGAAAGCCAATCCGCAT CATGTGGTCTCAGAGGGATCCCTCTTTGAGAAAATCTGGTGTGGGAAACGTCTTCATCAAGAAC CTGGACAAATCTATAGATAACAAGGCACTTTATGATACTTTTTCTGCTTTTGGAAACATACTGT CCTGCAAGGTGGTGTGTGATGAGAACGGCTCTAAGGGTTATGCCTTTGTCCACTTCGAGACCCA AGAGGCTGCCGACAAGGCCATCGAGAAGATGAATGGCATGCTCCTCAATGACCGCAAAGTATTT GTGGGCAGATTCAAGTCTCGCAAAGAGCGGGAAGCTGAGCTTGGAGCCAAAGCCAAGGAATTCA CCAATGTTTATATCAAAAACTTTGGGGAAGAGGTGGATGATGAGAGTCTGAAAGAGCTATTCAG TCAGTTTGGTAAGACCCTAAGTGTCAAGGTGATGAGAGATCCCAATGGGAAATCCAAAGGCTTT GGCTTTGTGAGTTACGAAAAACACGAGGATGCCAATAAGGCTGTGGAAGAGATGAATGGAAAAG AAATAAGTGGTAAAATCATATTTGTAGGCCGTGCACAAAAGAAAGTAGAACGGCAGGCAGAGTT AAAACGGAAATTTGAACAGTTGAAACAGGAGAGAATTAGTCGATATCAGGGGGTGAATCTCTAC ATTAAGAACTTGGATGACACTATTGATGATGAGAAATTAAGGAAAGAATTTTCTCCTTTTGGAT CAATTACCAGTGCTAAGGTAATGCTGGAGGATGGAAGAAGCAAAGGGTTTGGCTTCGTCTGCTT CTCATCTCCTGAAGAAGCAACCAAAGCAGTCACTGAGATGAATGGACGCATTGTGGGCTCCAAG CCACTATATGTTGCCCTGGCCCAGAGGAAGGAAGAGAGAAAGGCTCACCTGACCAACCAGTATA TGCAACGAGTGGCTGGAATGAGAGCACTTCCTGCCAATGCCATCTTAAATCAGTTCCAGCCTGC AGCGGGTGGCTACTTTGTGCCAGCAGTCCCACAGGCTCAGGGAAGGCCTCCATATTATACACCT AACCAGTTAGCACAGATGAGGCCTAATCCACGCTGGCAGCAAGGTGGGAGACCTCAAGGCTTCC AAGGAATGCCAAGTGCTATACGCCAGTCTGGGCCTCGTCCAACTCTTCGCCATCTGGCTCCAAC TGGTAATGCTCCGGCCTCTCGTGGCCTCCCTACTACCACTCAGAGAGTCGGCGTTCCCACAGCT GTGCAGAACTTAGCGCCACGCGCTGCTGTTGCTGCTGCTGCTCCCCGGGCTGTTGCCCCCTACA AATACGCCTCCAGTGTCCGCAGCCCTCATCCTGCCATACAGCCTCTGCAGGCACCCCAGCCTGC GGTCCATGTGCAGGGGCAGGAGCCACTGACTGCCTCCATGCTGGCTGCAGCACCCCCCCAGGAA CAGAAGCAGATGCTGGGAGAACGCTTGTTCCCACTCATCCAAACAATGCATTCAAATCTGGCTG GGAAGATCACGGGAATGCTGCTGGAGATAGACAACTCTGAGCTGCTGCACATGTTAGAGTCCCC CGAGTCTCTCCGCTCCAAGGTGGATGAAGCTGTAGCAGTTCTACAGGCTCATCATGCCAAGAAA GAAGCTGCCCAGAAGGTGGGCGCTGTTGCTGCTGCTACCTCT

Premade Adenovirus with ORF of poly (A) binding protein, cytoplasmic 4 (inducible form) (PABPC4), transcript variant 1 with C terminal Flag and His tag.

ATGAACGCTGCGGCCAGCAGCTACCCCATGGCCTCCCTGTACGTGGGCGACCTGCATTC GGACGTCACCGAGGCCATGCTGTACGAAAAGTTCAGCCCCGCGGGGCCTGTGCTGTCCATCCGG GTCTGCCGCGATATGATCACCCGCCGCTCCCTGGGCTATGCCTACGTCAACTTCCAGCAGCCGG CCGACGCTGAGCGGGCTTTGGACACCATGAACTTTGATGTGATTAAGGGAAAGCCAATCCGCAT CATGTGGTCTCAGAGGGATCCCTCTTTGAGAAAATCTGGTGTGGGAAACGTCTTCATCAAGAAC CTGGACAAATCTATAGATAACAAGGCACTTTATGATACTTTTTCTGCTTTTGGAAACATACTGT CCTGCAAGGTGGTGTGTGATGAGAACGGCTCTAAGGGTTATGCCTTTGTCCACTTCGAGACCCA AGAGGCTGCCGACAAGGCCATCGAGAAGATGAATGGCATGCTCCTCAATGACCGCAAAGTATTT GTGGGCAGATTCAAGTCTCGCAAAGAGCGGGAAGCTGAGCTTGGAGCCAAAGCCAAGGAATTCA CCAATGTTTATATCAAAAACTTTGGGGAAGAGGTGGATGATGAGAGTCTGAAAGAGCTATTCAG TCAGTTTGGTAAGACCCTAAGTGTCAAGGTGATGAGAGATCCCAATGGGAAATCCAAAGGCTTT GGCTTTGTGAGTTACGAAAAACACGAGGATGCCAATAAGGCTGTGGAAGAGATGAATGGAAAAG AAATAAGTGGTAAAATCATATTTGTAGGCCGTGCACAAAAGAAAGTAGAACGGCAGGCAGAGTT AAAACGGAAATTTGAACAGTTGAAACAGGAGAGAATTAGTCGATATCAGGGGGTGAATCTCTAC ATTAAGAACTTGGATGACACTATTGATGATGAGAAATTAAGGAAAGAATTTTCTCCTTTTGGAT CAATTACCAGTGCTAAGGTAATGCTGGAGGATGGAAGAAGCAAAGGGTTTGGCTTCGTCTGCTT CTCATCTCCTGAAGAAGCAACCAAAGCAGTCACTGAGATGAATGGACGCATTGTGGGCTCCAAG CCACTATATGTTGCCCTGGCCCAGAGGAAGGAAGAGAGAAAGGCTCACCTGACCAACCAGTATA TGCAACGAGTGGCTGGAATGAGAGCACTTCCTGCCAATGCCATCTTAAATCAGTTCCAGCCTGC AGCGGGTGGCTACTTTGTGCCAGCAGTCCCACAGGCTCAGGGAAGGCCTCCATATTATACACCT

AACCAGTTAGCACAGATGAGGCCTAATCCACGCTGGCAGCAAGGTGGGAGACCTCAAGGCTTCC

AAGGAATGCCAAGTGCTATACGCCAGTCTGGGCCTCGTCCAACTCTTCGCCATCTGGCTCCAAC

TGGTAATGCTCCGGCCTCTCGTGGCCTCCCTACTACCACTCAGAGAGTCGGGTCTGAGTGCCCG

GACCGCTTGGCTATGGACTTTGGTGGGGCTGGTGCCGCCCAGCAAGGGCTGACTGACAGCTGCC

AGTCTGGAGGCGTTCCCACAGCTGTGCAGAACTTAGCGCCACGCGCTGCTGTTGCTGCTGCTGC

TCCCCGGGCTGTTGCCCCCTACAAATACGCCTCCAGTGTCCGCAGCCCTCATCCTGCCATACAG

CCTCTGCAGGCACCCCAGCCTGCGGTCCATGTGCAGGGGCAGGAGCCACTGACTGCCTCCATGC

TGGCTGCAGCACCCCCCCAGGAACAGAAGCAGATGCTGGGAGAACGCTTGTTCCCACTCATCCA

AACAATGCATTCAAATCTGGCTGGGAAGATCACGGGAATGCTGCTGGAGATAGACAACTCTGAG

CTGCTGCACATGTTAGAGTCCCCCGAGTCTCTCCGCTCCAAGGTGGATGAAGCTGTAGCAGTTC

TACAGGCTCATCATGCCAAGAAAGAAGCTGCCCAGAAGGTGGGCGCTGTTGCTGCTGCTACCTC

T

Premade Adenovirus with ORF of poly (A) binding protein, cytoplasmic 4-like (PABPC4L) with C terminal Flag and His tag.

ATGAGGGTGTTGCCTGAGCTGGGGGAGTCGTGTCTGAACTCCATTGCTTGGCCTTTGTG TGGTGATCCCGAGGCCTCCACACTTGAACCGGGCCAAAGCTGTGACCTAGTATCCCCCCACAGG GATTGCTCAAAGAACTCCAGGGGACAAACTCACAGTGGCAAGGACAAGGAGATGAATGTAGCAG CCAAGTACCGCATGGCCTCCCTGTATGTGGGTGACTTACATGCAGATGTCACCGAGGACCTGCT GTTCAGGAAGTTCAGCACTGTGGGGCCTGTGCTGTCCATCCGCATTTGCAGGGACCAGGTCACC CGCCGCTCTCTGGGCTATGCCTACGTGAACTTCTTGCAGCTGGCTGATGCCCAGAAGGCGCTGG ACACAATGAACTTTGACATCATAAAAGGCAAATCCATCCGTCTCATGTGGTCTCAGCGCGATGC CTACTTGAGGAGATCTGGAATTGGGAACGTATTCATCAAGAATCTGGACAAATCTATCGATAAC AAAACCCTTTATGAACATTTTTCAGCTTTTGGAAAGATCCTTTCCTCCAAGGTGATGAGTGATG ATCAAGGCTCCAAGGGCTATGCATTTGTGCACTTTCAGAACCAGAGTGCTGCAGACAGGGCCAT TGAGGAGATGAATGGAAAACTACTCAAGGGCTGCAAGGTGTTTGTTGGCAGATTCAAAAACCGA AAAGATCGTGAAGCTGAACTCAGAAGCAAAGCCAGTGAATTCACCAATGTTTACATAAAAAACT TTGGAGGTGACATGGATGATGAGAGATTGAAGGACGTTTTCAGCAAATATGGCAAAACTCTGAG TGTTAAGGTGATGACAGATTCCAGTGGGAAATCCAAAGGCTTTGGCTTTGTGAGTTTTGATAGC CATGAGGCTGCCAAGAAAGCTGTTGAAGAAATGAATGGAAGGGACATAAATGGGCAGCTGATTT TTGTAGGCCGGGCTCAAAAGAAAGTCGAGCGACAGGCTGAGTTAAAGCAAATGTTTGAGCAGCT GAAAAGGGAACGAATTCGTGGGTGCCAGGGGGTAAAACTCTATATTAAGAACCTTGATGACACC ATCGATGATGAAAAACTACGAAACGAATTTTCTTCATTTGGATCAATTAGCAGAGTTAAGGTAA TGCAGGAAGAGGGGCAGAGCAAAGGGTTTGGCTTGATCTGCTTCTCCTCTCCTGAGGATGCTAC TAAAGCAATGACTGAGATGAATGGCCGCATCTTGGGCTCCAAACCTCTTAGCATTGCCTTGGCC CAGAGACAC

Premade Adenovirus with ORF of poly (A) binding protein, cytoplasmic 4 (inducible form) (PABPC4), transcript variant 2 with C terminal Flag and His tag.

ATGAACGCTGCGGCCAGCAGCTACCCCATGGCCTCCCTGTACGTGGGCGACCTGCATTC GGACGTCACCGAGGCCATGCTGTACGAAAAGTTCAGCCCCGCGGGGCCTGTGCTGTCCATCCGG GTCTGCCGCGATATGATCACCCGCCGCTCCCTGGGCTATGCCTACGTCAACTTCCAGCAGCCGG CCGACGCTGAGCGGGCTTTGGACACCATGAACTTTGATGTGATTAAGGGAAAGCCAATCCGCAT CATGTGGTCTCAGAGGGATCCCTCTTTGAGAAAATCTGGTGTGGGAAACGTCTTCATCAAGAAC CTGGACAAATCTATAGATAACAAGGCACTTTATGATACTTTTTCTGCTTTTGGAAACATACTGT CCTGCAAGGTGGTGTGTGATGAGAACGGCTCTAAGGGTTATGCCTTTGTCCACTTCGAGACCCA AGAGGCTGCCGACAAGGCCATCGAGAAGATGAATGGCATGCTCCTCAATGACCGCAAAGTATTT GTGGGCAGATTCAAGTCTCGCAAAGAGCGGGAAGCTGAGCTTGGAGCCAAAGCCAAGGAATTCA CCAATGTTTATATCAAAAACTTTGGGGAAGAGGTGGATGATGAGAGTCTGAAAGAGCTATTCAG TCAGTTTGGTAAGACCCTAAGTGTCAAGGTGATGAGAGATCCCAATGGGAAATCCAAAGGCTTT GGCTTTGTGAGTTACGAAAAACACGAGGATGCCAATAAGGCTGTGGAAGAGATGAATGGAAAAG AAATAAGTGGTAAAATCATATTTGTAGGCCGTGCACAAAAGAAAGTAGAACGGCAGGCAGAGTT AAAACGGAAATTTGAACAGTTGAAACAGGAGAGAATTAGTCGATATCAGGGGGTGAATCTCTAC ATTAAGAACTTGGATGACACTATTGATGATGAGAAATTAAGGAAAGAATTTTCTCCTTTTGGAT CAATTACCAGTGCTAAGGTAATGCTGGAGGATGGAAGAAGCAAAGGGTTTGGCTTCGTCTGCTT CTCATCTCCTGAAGAAGCAACCAAAGCAGTCACTGAGATGAATGGACGCATTGTGGGCTCCAAG CCACTATATGTTGCCCTGGCCCAGAGGAAGGAAGAGAGAAAGGCTCACCTGACCAACCAGTATA TGCAACGAGTGGCTGGAATGAGAGCACTTCCTGCCAATGCCATCTTAAATCAGTTCCAGCCTGC AGCGGGTGGCTACTTTGTGCCAGCAGTCCCACAGGCTCAGGGAAGGCCTCCATATTATACACCT AACCAGTTAGCACAGATGAGGCCTAATCCACGCTGGCAGCAAGGTGGGAGACCTCAAGGCTTCC AAGGAATGCCAAGTGCTATACGCCAGTCTGGGCCTCGTCCAACTCTTCGCCATCTGGCTCCAAC TGGGTCTGAGTGCCCGGACCGCTTGGCTATGGACTTTGGTGGGGCTGGTGCCGCCCAGCAAGGG CTGACTGACAGCTGCCAGTCTGGAGGCGTTCCCACAGCTGTGCAGAACTTAGCGCCACGCGCTG CTGTTGCTGCTGCTGCTCCCCGGGCTGTTGCCCCCTACAAATACGCCTCCAGTGTCCGCAGCCC TCATCCTGCCATACAGCCTCTGCAGGCACCCCAGCCTGCGGTCCATGTGCAGGGGCAGGAGCCA CTGACTGCCTCCATGCTGGCTGCAGCACCCCCCCAGGAACAGAAGCAGATGCTGGGAGAACGCT TGTTCCCACTCATCCAAACAATGCATTCAAATCTGGCTGGGAAGATCACGGGAATGCTGCTGGA GATAGACAACTCTGAGCTGCTGCACATGTTAGAGTCCCCCGAGTCTCTCCGCTCCAAGGTGGAT GAAGCTGTAGCAGTTCTACAGGCTCATCATGCCAAGAAAGAAGCTGCCCAGAAGGTGGGCGCTG TTGCTGCTGCTACCTCT

Ready-to-use lentiviral particle of poly (A) binding protein, cytoplasmic 4 (inducible form) (PABPC4), transcript variant 3 in pLent-SV40-Puro-CMV-FH, with C terminal Myc and Flag

ATGAACGCTGCGGCCAGCAGCTACCCCATGGCCTCCCTGTACGTGGGCGACCTGCATTC GGACGTCACCGAGGCCATGCTGTACGAAAAGTTCAGCCCCGCGGGGCCTGTGCTGTCCATCCGG GTCTGCCGCGATATGATCACCCGCCGCTCCCTGGGCTATGCCTACGTCAACTTCCAGCAGCCGG CCGACGCTGAGCGGGCTTTGGACACCATGAACTTTGATGTGATTAAGGGAAAGCCAATCCGCAT CATGTGGTCTCAGAGGGATCCCTCTTTGAGAAAATCTGGTGTGGGAAACGTCTTCATCAAGAAC CTGGACAAATCTATAGATAACAAGGCACTTTATGATACTTTTTCTGCTTTTGGAAACATACTGT CCTGCAAGGTGGTGTGTGATGAGAACGGCTCTAAGGGTTATGCCTTTGTCCACTTCGAGACCCA AGAGGCTGCCGACAAGGCCATCGAGAAGATGAATGGCATGCTCCTCAATGACCGCAAAGTATTT GTGGGCAGATTCAAGTCTCGCAAAGAGCGGGAAGCTGAGCTTGGAGCCAAAGCCAAGGAATTCA CCAATGTTTATATCAAAAACTTTGGGGAAGAGGTGGATGATGAGAGTCTGAAAGAGCTATTCAG TCAGTTTGGTAAGACCCTAAGTGTCAAGGTGATGAGAGATCCCAATGGGAAATCCAAAGGCTTT GGCTTTGTGAGTTACGAAAAACACGAGGATGCCAATAAGGCTGTGGAAGAGATGAATGGAAAAG AAATAAGTGGTAAAATCATATTTGTAGGCCGTGCACAAAAGAAAGTAGAACGGCAGGCAGAGTT AAAACGGAAATTTGAACAGTTGAAACAGGAGAGAATTAGTCGATATCAGGGGGTGAATCTCTAC ATTAAGAACTTGGATGACACTATTGATGATGAGAAATTAAGGAAAGAATTTTCTCCTTTTGGAT CAATTACCAGTGCTAAGGTAATGCTGGAGGATGGAAGAAGCAAAGGGTTTGGCTTCGTCTGCTT CTCATCTCCTGAAGAAGCAACCAAAGCAGTCACTGAGATGAATGGACGCATTGTGGGCTCCAAG CCACTATATGTTGCCCTGGCCCAGAGGAAGGAAGAGAGAAAGGCTCACCTGACCAACCAGTATA TGCAACGAGTGGCTGGAATGAGAGCACTTCCTGCCAATGCCATCTTAAATCAGTTCCAGCCTGC AGCGGGTGGCTACTTTGTGCCAGCAGTCCCACAGGCTCAGGGAAGGCCTCCATATTATACACCT AACCAGTTAGCACAGATGAGGCCTAATCCACGCTGGCAGCAAGGTGGGAGACCTCAAGGCTTCC AAGGAATGCCAAGTGCTATACGCCAGTCTGGGCCTCGTCCAACTCTTCGCCATCTGGCTCCAAC TGGTAATGCTCCGGCCTCTCGTGGCCTCCCTACTACCACTCAGAGAGTCGGCGTTCCCACAGCT GTGCAGAACTTAGCGCCACGCGCTGCTGTTGCTGCTGCTGCTCCCCGGGCTGTTGCCCCCTACA AATACGCCTCCAGTGTCCGCAGCCCTCATCCTGCCATACAGCCTCTGCAGGCACCCCAGCCTGC GGTCCATGTGCAGGGGCAGGAGCCACTGACTGCCTCCATGCTGGCTGCAGCACCCCCCCAGGAA CAGAAGCAGATGCTGGGAGAACGCTTGTTCCCACTCATCCAAACAATGCATTCAAATCTGGCTG GGAAGATCACGGGAATGCTGCTGGAGATAGACAACTCTGAGCTGCTGCACATGTTAGAGTCCCC CGAGTCTCTCCGCTCCAAGGTGGATGAAGCTGTAGCAGTTCTACAGGCTCATCATGCCAAGAAA

GAAGCTGCCCAGAAGGTGGGCGCTGTTGCTGCTGCTACCTCT

Ready-to-use lentiviral particle of poly (A) binding protein, cytoplasmic 4 (inducible form) (PABPC4), transcript variant 1 in pLent-SV40-Puro-CMV-FH, with C terminal Myc and Flag.

ATGAACGCTGCGGCCAGCAGCTACCCCATGGCCTCCCTGTACGTGGGCGACCTGCATTC GGACGTCACCGAGGCCATGCTGTACGAAAAGTTCAGCCCCGCGGGGCCTGTGCTGTCCATCCGG GTCTGCCGCGATATGATCACCCGCCGCTCCCTGGGCTATGCCTACGTCAACTTCCAGCAGCCGG CCGACGCTGAGCGGGCTTTGGACACCATGAACTTTGATGTGATTAAGGGAAAGCCAATCCGCAT CATGTGGTCTCAGAGGGATCCCTCTTTGAGAAAATCTGGTGTGGGAAACGTCTTCATCAAGAAC CTGGACAAATCTATAGATAACAAGGCACTTTATGATACTTTTTCTGCTTTTGGAAACATACTGT CCTGCAAGGTGGTGTGTGATGAGAACGGCTCTAAGGGTTATGCCTTTGTCCACTTCGAGACCCA AGAGGCTGCCGACAAGGCCATCGAGAAGATGAATGGCATGCTCCTCAATGACCGCAAAGTATTT GTGGGCAGATTCAAGTCTCGCAAAGAGCGGGAAGCTGAGCTTGGAGCCAAAGCCAAGGAATTCA CCAATGTTTATATCAAAAACTTTGGGGAAGAGGTGGATGATGAGAGTCTGAAAGAGCTATTCAG TCAGTTTGGTAAGACCCTAAGTGTCAAGGTGATGAGAGATCCCAATGGGAAATCCAAAGGCTTT GGCTTTGTGAGTTACGAAAAACACGAGGATGCCAATAAGGCTGTGGAAGAGATGAATGGAAAAG AAATAAGTGGTAAAATCATATTTGTAGGCCGTGCACAAAAGAAAGTAGAACGGCAGGCAGAGTT AAAACGGAAATTTGAACAGTTGAAACAGGAGAGAATTAGTCGATATCAGGGGGTGAATCTCTAC ATTAAGAACTTGGATGACACTATTGATGATGAGAAATTAAGGAAAGAATTTTCTCCTTTTGGAT CAATTACCAGTGCTAAGGTAATGCTGGAGGATGGAAGAAGCAAAGGGTTTGGCTTCGTCTGCTT CTCATCTCCTGAAGAAGCAACCAAAGCAGTCACTGAGATGAATGGACGCATTGTGGGCTCCAAG CCACTATATGTTGCCCTGGCCCAGAGGAAGGAAGAGAGAAAGGCTCACCTGACCAACCAGTATA TGCAACGAGTGGCTGGAATGAGAGCACTTCCTGCCAATGCCATCTTAAATCAGTTCCAGCCTGC AGCGGGTGGCTACTTTGTGCCAGCAGTCCCACAGGCTCAGGGAAGGCCTCCATATTATACACCT AACCAGTTAGCACAGATGAGGCCTAATCCACGCTGGCAGCAAGGTGGGAGACCTCAAGGCTTCC AAGGAATGCCAAGTGCTATACGCCAGTCTGGGCCTCGTCCAACTCTTCGCCATCTGGCTCCAAC TGGTAATGCTCCGGCCTCTCGTGGCCTCCCTACTACCACTCAGAGAGTCGGGTCTGAGTGCCCG GACCGCTTGGCTATGGACTTTGGTGGGGCTGGTGCCGCCCAGCAAGGGCTGACTGACAGCTGCC AGTCTGGAGGCGTTCCCACAGCTGTGCAGAACTTAGCGCCACGCGCTGCTGTTGCTGCTGCTGC TCCCCGGGCTGTTGCCCCCTACAAATACGCCTCCAGTGTCCGCAGCCCTCATCCTGCCATACAG CCTCTGCAGGCACCCCAGCCTGCGGTCCATGTGCAGGGGCAGGAGCCACTGACTGCCTCCATGC TGGCTGCAGCACCCCCCCAGGAACAGAAGCAGATGCTGGGAGAACGCTTGTTCCCACTCATCCA AACAATGCATTCAAATCTGGCTGGGAAGATCACGGGAATGCTGCTGGAGATAGACAACTCTGAG CTGCTGCACATGTTAGAGTCCCCCGAGTCTCTCCGCTCCAAGGTGGATGAAGCTGTAGCAGTTC TACAGGCTCATCATGCCAAGAAAGAAGCTGCCCAGAAGGTGGGCGCTGTTGCTGCTGCTACCTC T

The titer of lentivirus is very sensitive to the size of viral genome. Offered titer is based on that the viral genome, insert between two LTRs, is less than 5.1kb. And the gene of interest is less than 1.5kb. Every kb increases of the viral genome, the titer will be decreased by 10 times. Genome copy (GC) is measured by real-time qPCR of lentivirus; infection unit (IU) is measured by fluorescent microcopy of GFP expressing cells.

Ready-to-use lentiviral particle of poly (A) binding protein, cytoplasmic 4-like (PABPC4L) in pLent-SV40-Puro-CMV-FH, with C terminal Myc and Flag.

Ready-to-use lentiviral particle of poly (A) binding protein, cytoplasmic 4 (inducible form) (PABPC4), transcript variant 2 in pLent-SV40-Puro-CMV-FH, with C terminal Myc and Flag. ATGAACGCTGCGGCCAGCAGCTACCCCATGGCCTCCCTGTACGTGGGCGACCTGCATTC GGACGTCACCGAGGCCATGCTGTACGAAAAGTTCAGCCCCGCGGGGCCTGTGCTGTCCATCCGG GTCTGCCGCGATATGATCACCCGCCGCTCCCTGGGCTATGCCTACGTCAACTTCCAGCAGCCGG CCGACGCTGAGCGGGCTTTGGACACCATGAACTTTGATGTGATTAAGGGAAAGCCAATCCGCAT CATGTGGTCTCAGAGGGATCCCTCTTTGAGAAAATCTGGTGTGGGAAACGTCTTCATCAAGAAC CTGGACAAATCTATAGATAACAAGGCACTTTATGATACTTTTTCTGCTTTTGGAAACATACTGT CCTGCAAGGTGGTGTGTGATGAGAACGGCTCTAAGGGTTATGCCTTTGTCCACTTCGAGACCCA AGAGGCTGCCGACAAGGCCATCGAGAAGATGAATGGCATGCTCCTCAATGACCGCAAAGTATTT GTGGGCAGATTCAAGTCTCGCAAAGAGCGGGAAGCTGAGCTTGGAGCCAAAGCCAAGGAATTCA CCAATGTTTATATCAAAAACTTTGGGGAAGAGGTGGATGATGAGAGTCTGAAAGAGCTATTCAG TCAGTTTGGTAAGACCCTAAGTGTCAAGGTGATGAGAGATCCCAATGGGAAATCCAAAGGCTTT GGCTTTGTGAGTTACGAAAAACACGAGGATGCCAATAAGGCTGTGGAAGAGATGAATGGAAAAG AAATAAGTGGTAAAATCATATTTGTAGGCCGTGCACAAAAGAAAGTAGAACGGCAGGCAGAGTT AAAACGGAAATTTGAACAGTTGAAACAGGAGAGAATTAGTCGATATCAGGGGGTGAATCTCTAC ATTAAGAACTTGGATGACACTATTGATGATGAGAAATTAAGGAAAGAATTTTCTCCTTTTGGAT CAATTACCAGTGCTAAGGTAATGCTGGAGGATGGAAGAAGCAAAGGGTTTGGCTTCGTCTGCTT CTCATCTCCTGAAGAAGCAACCAAAGCAGTCACTGAGATGAATGGACGCATTGTGGGCTCCAAG CCACTATATGTTGCCCTGGCCCAGAGGAAGGAAGAGAGAAAGGCTCACCTGACCAACCAGTATA TGCAACGAGTGGCTGGAATGAGAGCACTTCCTGCCAATGCCATCTTAAATCAGTTCCAGCCTGC AGCGGGTGGCTACTTTGTGCCAGCAGTCCCACAGGCTCAGGGAAGGCCTCCATATTATACACCT AACCAGTTAGCACAGATGAGGCCTAATCCACGCTGGCAGCAAGGTGGGAGACCTCAAGGCTTCC AAGGAATGCCAAGTGCTATACGCCAGTCTGGGCCTCGTCCAACTCTTCGCCATCTGGCTCCAAC TGGGTCTGAGTGCCCGGACCGCTTGGCTATGGACTTTGGTGGGGCTGGTGCCGCCCAGCAAGGG CTGACTGACAGCTGCCAGTCTGGAGGCGTTCCCACAGCTGTGCAGAACTTAGCGCCACGCGCTG CTGTTGCTGCTGCTGCTCCCCGGGCTGTTGCCCCCTACAAATACGCCTCCAGTGTCCGCAGCCC TCATCCTGCCATACAGCCTCTGCAGGCACCCCAGCCTGCGGTCCATGTGCAGGGGCAGGAGCCA CTGACTGCCTCCATGCTGGCTGCAGCACCCCCCCAGGAACAGAAGCAGATGCTGGGAGAACGCT TGTTCCCACTCATCCAAACAATGCATTCAAATCTGGCTGGGAAGATCACGGGAATGCTGCTGGA GATAGACAACTCTGAGCTGCTGCACATGTTAGAGTCCCCCGAGTCTCTCCGCTCCAAGGTGGAT GAAGCTGTAGCAGTTCTACAGGCTCATCATGCCAAGAAAGAAGCTGCCCAGAAGGTGGGCGCTG TTGCTGCTGCTACCTCT

TRIM58

Premade Adenovirus with ORF of tripartite motif containing 58 (TRIM58) with C terminal Flag and His tag.

ATGGCCTGGGCGCCGCCCGGGGAGCGGCTGCGCGAGGATGCGCGGTGCCCGGTGTGCCT GGATTTCCTGCAGGAGCCGGTCAGCGTGGACTGCGGCCACAGCTTCTGCCTCAGGTGCATCTCC GAGTTCTGCGAGAAGTCGGACGGCGCGCAGGGCGGCGTCTACGCCTGTCCGCAGTGCCGGGGCC CCTTCCGGCCCTCGGGCTTTCGCCCCAACCGGCAGCTGGCGGGCCTGGTGGAGAGCGTGCGGCG GCTGGGGTTGGGCGCGGGGCCCGGGGCGCGGCGATGCGCGCGGCACGGCGAGGACCTGAGCCGC TTCTGCGAGGAGGACGAGGCGGCGCTGTGCTGGGTGTGCGACGCCGGCCCCGAGCACAGGACGC ACCGCACGGCGCCGCTGCAGGAGGCCGCCGGCAGCTACCAGGTAAAGCTCCAGATGGCTCTGGA ACTTATGAGGAAAGAGTTGGAGGACGCCTTGACTCAGGAGGCCAACGTGGGGAAAAAGACTGTC ATTTGGAAGGAGAAAGTGGAAATGCAGAGGCAGCGCTTCAGATTGGAGTTTGAGAAGCATCGTG GCTTTCTGGCCCAGGAGGAGCAACGGCAGCTGAGGCGGCTGGAGGCGGAGGAGCGAGCGACGCT GCAGAGACTGCGGGAGAGCAAGAGCCGGCTGGTCCAGCAGAGCAAGGCCCTGAAGGAGCTGGCG GATGAGCTGCAGGAGAGGTGCCAGCGCCCGGCCCTGGGTCTGCTGGAGGGTGTGAGAGGAGTCC TGAGCAGAAGTAAGGCTGTCACAAGGCTGGAAGCAGAGAACATCCCCATGGAACTGAAGACAGC ATGCTGCATCCCTGGGAGGAGGGAGCTCTTAAGGAAGTTCCAAGTGGATGTAAAGCTGGATCCC GCCACGGCGCACCCGAGTCTGCTCTTGACCGCCGACCTGCGCAGTGTGCAGGATGGAGAACCAT GGAGGGATGTCCCCAACAACCCTGAGCGATTTGACACATGGCCCTGCATCCTGGGTTTGCAGAG CTTCTCATCAGGGAGGCATTACTGGGAGGTTCTGGTGGGAGAAGGAGCAGAGTGGGGTTTAGGG GTCTGTCAAGACACACTGCCAAGAAAGGGGGAAACCACGCCATCTCCTGAGAATGGGGTCTGGG

CCCTGTGGCTGCTGAAAGGGAATGAGTACATGGTCCTTGCCTCCCCATCAGTGCCTCTTCTCCA

ACTGGAAAGTCCTCGCTGCATTGGGATTTTCTTGGACTATGAAGCCGGTGAAATTTCATTCTAC

AATGTCACAGATGGATCTTATATCTACACATTCAACCAACTCTTCTCTGGTCTTCTTCGGCCTT

ACTTTTTCATCTGTGATGCAACTCCTCTTATCTTGCCACCCACAACAATAGCAGGGTCAGGAAA

TTGGGCATCCAGGGATCATTTAGATCCTGCTTCTGATGTAAGAGATGATCATCTC

Ready-to-use lentiviral particle of tripartite motif containing 58 (TRIM58) in pLent-SV4 O-Puro-CMV-FH, with C terminal Myc and Flag.

ATGGCCTGGGCGCCGCCCGGGGAGCGGCTGCGCGAGGATGCGCGGTGCCCGGTGTGCCT GGATTTCCTGCAGGAGCCGGTCAGCGTGGACTGCGGCCACAGCTTCTGCCTCAGGTGCATCTCC GAGTTCTGCGAGAAGTCGGACGGCGCGCAGGGCGGCGTCTACGCCTGTCCGCAGTGCCGGGGCC CCTTCCGGCCCTCGGGCTTTCGCCCCAACCGGCAGCTGGCGGGCCTGGTGGAGAGCGTGCGGCG GCTGGGGTTGGGCGCGGGGCCCGGGGCGCGGCGATGCGCGCGGCACGGCGAGGACCTGAGCCGC TTCTGCGAGGAGGACGAGGCGGCGCTGTGCTGGGTGTGCGACGCCGGCCCCGAGCACAGGACGC ACCGCACGGCGCCGCTGCAGGAGGCCGCCGGCAGCTACCAGGTAAAGCTCCAGATGGCTCTGGA ACTTATGAGGAAAGAGTTGGAGGACGCCTTGACTCAGGAGGCCAACGTGGGGAAAAAGACTGTC ATTTGGAAGGAGAAAGTGGAAATGCAGAGGCAGCGCTTCAGATTGGAGTTTGAGAAGCATCGTG GCTTTCTGGCCCAGGAGGAGCAACGGCAGCTGAGGCGGCTGGAGGCGGAGGAGCGAGCGACGCT GCAGAGACTGCGGGAGAGCAAGAGCCGGCTGGTCCAGCAGAGCAAGGCCCTGAAGGAGCTGGCG GATGAGCTGCAGGAGAGGTGCCAGCGCCCGGCCCTGGGTCTGCTGGAGGGTGTGAGAGGAGTCC TGAGCAGAAGTAAGGCTGTCACAAGGCTGGAAGCAGAGAACATCCCCATGGAACTGAAGACAGC ATGCTGCATCCCTGGGAGGAGGGAGCTCTTAAGGAAGTTCCAAGTGGATGTAAAGCTGGATCCC GCCACGGCGCACCCGAGTCTGCTCTTGACCGCCGACCTGCGCAGTGTGCAGGATGGAGAACCAT GGAGGGATGTCCCCAACAACCCTGAGCGATTTGACACATGGCCCTGCATCCTGGGTTTGCAGAG CTTCTCATCAGGGAGGCATTACTGGGAGGTTCTGGTGGGAGAAGGAGCAGAGTGGGGTTTAGGG GTCTGTCAAGACACACTGCCAAGAAAGGGGGAAACCACGCCATCTCCTGAGAATGGGGTCTGGG CCCTGTGGCTGCTGAAAGGGAATGAGTACATGGTCCTTGCCTCCCCATCAGTGCCTCTTCTCCA ACTGGAAAGTCCTCGCTGCATTGGGATTTTCTTGGACTATGAAGCCGGTGAAATTTCATTCTAC AATGTCACAGATGGATCTTATATCTACACATTCAACCAACTCTTCTCTGGTCTTCTTCGGCCTT ACTTTTTCATCTGTGATGCAACTCCTCTTATCTTGCCACCCACAACAATAGCAGGGTCAGGAAA TTGGGCATCCAGGGATCATTTAGATCCTGCTTCTGATGTAAGAGATGATCATCTC

MSRA

Premade Adenovirus with ORF of methionine sulfoxide reductase A (MSRA), transcript variant 3 with C terminal Flag and His tag.

ATGTGTTCAGAACCCAAACATCATGTCAATGGCAACAGAACAGTCGAACCTTTCCCAGA GGGAACACAGATGGCTGTATTTGGAATGGGATGTTTCTGGGGAGCTGAAAGGAAATTCTGGGTC TTGAAAGGAGTGTATTCAACTCAAGTTGGTTTTGCAGGAGGCTATACTTCAAATCCTACTTATA AAGAAGTCTGCTCAGAAAAAACTGGCCATGCAGAAGTCGTCCGAGTGGTGTACCAGCCAGAACA CATGAGTTTTGAGGAACTGCTCAAGGTCTTCTGGGAGAATCACGACCCGACCCAAGGTATGCGC CAGGGGAACGACCATGGCACTCAGTACCGCTCGGCCATCTACCCGACCTCTGCCAAGCAAATGG AGGCAGCCCTGAGCTCCAAAGAGAACTACCAAAAGGTTCTTTCAGAGCACGGCTTCGGCCCCAT CACTACCGACATCCGGGAGGGACAGACTTTCTACTATGCGGAAGACTACCACCAGCAGTACCTG AGCAAGAACCCCAATGGCTACTGCGGCCTTGGGGGCACCGGCGTGTCCTGCCCAGTGGGTATTA AAAAA

Premade Adenovirus with ORF of methionine sulfoxide reductase A (MSRA), transcript variant 1 with C terminal Flag and His tag. CGCCATGCTCTCGGCCACccggagggcttgccAGCTCCTCCTCCTCCACAGCCTCTTTC CCGTCCCGAGGATGGGCAACTCGGCCTCGAACATCGTCAGCCCCCAGGAGGCCTTGCCGGGCCG GAAGGAACAGACCCCTGTAGCGGCCAAACATCATGTCAATGGCAACAGAACAGTCGAACCTTTC CCAGAGGGAACACAGATGGctgtatttggaatgGGATGTTTCTGGGGAGCTGAAAGGAAATTCT GGGTCTTGAAAGGAGTGTATTCAACTCAAGTTGGTTTTGCAGGAGGCTATACTTCAAATCCTAC TTATAAAGAAGTCTGCTCAGAAAAAACTGGCCATGCAGAAGTCGTCCGAGTGGTGTACCAGCCA GAACACATGAGTTTTGAGGAACTGCTCAAGGTCTTCTGGGAGAATCACGAcccgacccaaggta TGCGCCAGGGGAACGACCATGGCACTCAGTACCGCTCGGCCatctacccgacctcTGCCAAGCA AATGGAggcagccctgagctCCAAAGAGAACTACCAAAAGGTTCTTTCAGAGCACGGCTTCGGC CCCATCACTACCGACATCCGGGAGGGACAGACTTTCTACTATGCGGAAGACTACCACCAGCAGT ACCTGAGCAAGAACCCCAATGGCTACTGCGGCCTTGGGGGCACCGGCGTGTCCTGCCCAGTGGG TATTaaaaaaa

Premade Adenovirus with ORF of methionine sulfoxide reductase A (MSRA) , transcript variant 4 with C terminal Flag and His tag

ATGGCTGTATTTGGAATGGGATGTTTCTGGGGAGCTGAAAGGAAATTCTGGGTCTTGAA AGGAGTGTATTCAACTCAAGTTGGTTTTGCAGGAGGCTATACTTCAAATCCTACTTATAAAGAA GTCTGCTCAGAAAAAACTGGCCATGCAGAAGTCGTCCGAGTGGTGTACCAGCCAGAACACATGA GTTTTGAGGAACTGCTCAAGGTCTTCTGGGAGAATCACGACCCGACCCAAGGTATGCGCCAGGG GAACGACCATGGCACTCAGTACCGCTCGGCCATCTACCCGACCTCTGCCAAGCAAATGGAGGCA GCCCTGAGCTCCAAAGAGAACTACCAAAAGGTTCTTTCAGAGCACGGCTTCGGCCCCATCACTA CCGACATCCGGGAGGGACAGACTTTCTACTATGCGGAAGACTACCACCAGCAGTACCTGAGCAA GAACCCCAATGGCTACTGCGGCCTTGGGGGCACCGGCGTGTCCTGCCCAGTGGGTATTAAAAAA

Premade Adenovirus with ORF of methionine sulfoxide reductase A (MSRA), transcript variant 2 with C terminal Flag and His tag.

ATGCTCTCGGCCACCCGGAGGGCTTGCCAGCTCCTCCTCCTCCACAGCCTCTTTCCCGT CCCGAGGATGGGCAACTCGGCCTCGAACATCGTCAGCCCCCAGGAGGCCTTGCCGGGCCGGAAG GAACAGACCCCTGTAGCGGCCAAACATCATGTCAATGGCAACAGAACAGTCGAACCTTTCCCAG AGGGAACACAGATGGCTGTATTTGAAAAAACTGGCCATGCAGAAGTCGTCCGAGTGGTGTACCA GCCAGAACACATGAGTTTTGAGGAACTGCTCAAGGTCTTCTGGGAGAATCACGACCCGACCCAA GGTATGCGCCAGGGGAACGACCATGGCACTCAGTACCGCTCGGCCATCTACCCGACCTCTGCCA AGCAAATGGAGGCAGCCCTGAGCTCCAAAGAGAACTACCAAAAGGTTCTTTCAGAGCACGGCTT CGGCCCCATCACTACCGACATCCGGGAGGGACAGACTTTCTACTATGCGGAAGACTACCACCAG CAGTACCTGAGCAAGAACCCCAATGGCTACTGCGGCCTTGGGGGCACCGGCGTGTCCTGCCCAG TGGGTATTAAAAAA

Ready-to-use lentiviral particle of methionine sulfoxide reductase A (MSRA) , transcript variant 3 in pLent-SV40-Puro-CMV- FH, with C terminal Myc and Flag.

ATGTGTTCAGAACCCAAACATCATGTCAATGGCAACAGAACAGTCGAACCTTTCCCAGA GGGAACACAGATGGCTGTATTTGGAATGGGATGTTTCTGGGGAGCTGAAAGGAAATTCTGGGTC TTGAAAGGAGTGTATTCAACTCAAGTTGGTTTTGCAGGAGGCTATACTTCAAATCCTACTTATA AAGAAGTCTGCTCAGAAAAAACTGGCCATGCAGAAGTCGTCCGAGTGGTGTACCAGCCAGAACA CATGAGTTTTGAGGAACTGCTCAAGGTCTTCTGGGAGAATCACGACCCGACCCAAGGTATGCGC CAGGGGAACGACCATGGCACTCAGTACCGCTCGGCCATCTACCCGACCTCTGCCAAGCAAATGG AGGCAGCCCTGAGCTCCAAAGAGAACTACCAAAAGGTTCTTTCAGAGCACGGCTTCGGCCCCAT CACTACCGACATCCGGGAGGGACAGACTTTCTACTATGCGGAAGACTACCACCAGCAGTACCTG AGCAAGAACCCCAATGGCTACTGCGGCCTTGGGGGCACCGGCGTGTCCTGCCCAGTGGGTATTA AAAAA Ready-to-use lentiviral particle of methionine sulfoxide reductase A (MSRA) , transcript variant 1 in pLent-SV40-Puro-CMV- FH, with C terminal Myc and Flag.

CGCCATGCTCTCGGCCACccggagggcttgccAGCTCCTCCTCCTCCACAGCCTCTTTC CCGTCCCGAGGATGGGCAACTCGGCCTCGAACATCGTCAGCCCCCAGGAGGCCTTGCCGGGCCG GAAGGAACAGACCCCTGTAGCGGCCAAACATCATGTCAATGGCAACAGAACAGTCGAACCTTTC CCAGAGGGAACACAGATGGctgtatttggaatgGGATGTTTCTGGGGAGCTGAAAGGAAATTCT GGGTCTTGAAAGGAGTGTATTCAACTCAAGTTGGTTTTGCAGGAGGCTATACTTCAAATCCTAC TTATAAAGAAGTCTGCTCAGAAAAAACTGGCCATGCAGAAGTCGTCCGAGTGGTGTACCAGCCA GAACACATGAGTTTTGAGGAACTGCTCAAGGTCTTCTGGGAGAATCACGAcccgacccaaggta TGCGCCAGGGGAACGACCATGGCACTCAGTACCGCTCGGCCatctacccgacctcTGCCAAGCA AATGGAggcagccctgagctCCAAAGAGAACTACCAAAAGGTTCTTTCAGAGCACGGCTTCGGC CCCATCACTACCGACATCCGGGAGGGACAGACTTTCTACTATGCGGAAGACTACCACCAGCAGT ACCTGAGCAAGAACCCCAATGGCTACTGCGGCCTTGGGGGCACCGGCGTGTCCTGCCCAGTGGG TATTaaaaaaa

Ready-to-use lentiviral particle of methionine sulfoxide reductase A (MSRA) , transcript variant 4 in pLent-SV40-Puro-CMV- FH, with C terminal Myc and Flag.

Ready-to-use lentiviral particle of methionine sulfoxide reductase A (MSRA) , transcript variant 2 in pLent-SV40-Puro-CMV- FH, with C terminal Myc and Flag.

IREB2

Premade Adenovirus with ORF of iron-responsive element binding protein 2 (IREB2) with C terminal Flag and His tag. AT G GAC G C C C C AAAAG C AG GAT AC G C C T T T GAG T AC C T T AT T GAAAC AT T AAAT GAC AG TTCACATAAGAAGTTCTTCGATGTATCTAAACTTGGCACCAAGTATGATGTTCTGCCTTACTCA ATACGGGTCTTGTTGGAAGCTGCTGTACGAAATTGTGATGGCTTTTTAATGAAGAAGGAAGATG TTATGAACATTTTAGACTGGAAAACCAAACAAAGCAATGTTGAAGTGCCCTTTTTCCCTGCCCG TGTTCTTCTTCAAGATTTTACTGGAATACCAGCAATGGTGGATTTTGCTGCTATGAGGGAGGCA GTGAAAACTCTTGGAGGTGATCCTGAGAAAGTCCATCCTGCTTGTCCGACAGATCTTACAGTTG AC CAT T C T T T AC AAAT T GAC T T C AG T AAAT G T G C AAT AC AGAAT G C AC CAAAT C C T G GAG G T G G TGACCTGCAGAAAGCAGGAAAGCTCTCTCCACTTAAAGTGCAGCCTAAGAAGCTTCCCTGCAGA GGCCAGACTACCTGCCGAGGATCTTGTGATTCTGGAGAACTAGGCCGAAACTCAGGAACATTTT CTTCGCAGATTGAGAATACACCCATCCTGTGTCCTTTTCATTTGCAACCAGTGCCTGAACCTGA AAC AG T G T T AAAAAAT CAAGAAG T AGAAT T C G G CAGAAAT C GAGAGAG GC T T C AG T T T T T TAAG TGGAGTTCAAGAGTTTTTAAGAATGTGGCAGTGATCCCTCCTGGAACTGGAATGGCTCATCAAA T AAAC T T AGAAT AT T T G T C AAGAG T G G T T T T T GAAGAAAAAGAC C T C C T C T T C C C AGAC AG T G T AGTCGGCACAGATTCACACATAACGATGGTGAATGGTTTAGGGATTCTGGGGTGGGGGGTTGGA GGCATTGAAACAGAAGCAGTTATGCTTGGTCTGCCAGTTTCTCTTACTTTACCAGAGGTGGTTG GATGTGAGTTAACTGGGTCATCAAACCCTTTTGTTACATCCATAGATGTTGTTCTTGGTATTAC AAAGCACCTCAGGCAAGTAGGAGTGGCTGGAAAGTTTGTTGAGTTTTTTGGAAGTGGAGTTTCA C AAT T AT C TAT AG T T GAT C GAAC T AC AAT AG C AAAC AT G T G T C C G GAAT AT GGTGCTATCCTCA GCTTTTTCCCTGTT GAC AAT G T GAC AT T AAAAC AT T T AGAAC AT AC AG G T T T TAG C AAAG C C AA AC T C GAAT C AAT G GAAAC AT AC C T T AAAG C T G T GAAAT T G T T T C GAAAT GAC C AGAAT T C T T C A G GAGAAC C T GAAT AC T C C C AG G T GAT C C AGAT T AAT C T GAAT T C AAT AG TTCCATCTGTTAGTG G T C C AAAAAGAC C T C AG GAT AGAG T T G C T G T GAC AGAT AT GAAAAG C GAT T T C C AG GCTTGCTT AAAT GAAAAGGT T GGAT T TAAAGGC T T CCAAAT T GCAGC T GAAAAAC AAAAG GAT AT T GT C T CC ATT CAT TAT GAAG GAAG T GAAT AT AAG C T G T C T CAT G GAT C AG T G G T CAT T G C T G C AG T T AT C A GTTGTACCAATAATTGCAATCCATCTGTCATGCTTGCTGCAGGTCTTTTGGCTAAAAAGGCTGT TGAAGCTGGTCTGCGTGTTAAACCTTATATAAGAACAAGTTTATCTCCAGGCAGTGGGATGGTT AC AC AT T AC C T C AG T T C AAG T G GAG TAT T AC CAT AT C TAAG TAAG CTTGGATTT GAAAT C G T T G GCTATGGATGTTCAACTTGTGTGGGAAATACAGCACCCTTATCAGACGCAGTTTTAAATGCAGT AAAACAGGGTGATTTGGTTACCTGTGGAATTTTATCTGGAAACAAAAATTTTGAAGGTCGTCTT TGTGATTGTGTTCGTGCCAATTATCTTGCCTCTCCACCCTTAGTGGTAGCTTATGCCATAGCAG G C AC AG T GAAT AT AGAT T T C C AGAC AGAAC C T T TAG G T AC T GAC C C C AC C G G C AAGAAC AT T T A CCTGCATGATATTTGGCCTAGTC GAGAAGAAG T T C AT C GAG T AGAG GAAGAAC AT GTTATACTA T C CAT G T T T AAAG CAT T AAAAGAT AAAAT AGAAAT G G G GAAT AAAC G G T G GAAT T C C T T AGAAG CACCGGATTCAGTTTTGTTTCCATGGGACTTAAAGTCTACTTATATCAGATGCCCTTCATTTTT T GAT AAAC T T AC C AAAGAG C C AAT T G C AC T C C AG G C T AT T GAAAAT G C C CAT GTCTTATTATAT T T G G GAGAC T C T G T C AC AAC AGAT CAT AT AT C AC C T G C AG GAAG T AT C GC TAG GAAT AG T G C T G CCGCTAAGTATTTGACAAACAGAGGCCTTACCCCTCGTGAATTCAACTCTTACGGAGCTCGAAG AGGTAAT GAT GC T GTAAT GAC AAG AG G C AC T T T T GCAAATAT CAAGCT T T T TAATAAGT T TAT T G GAAAAC C AG C T C C T AAAAC AAT T CAT T T T C CAT C AG GAC AGAC G C T AGAT G T AT T T GAG G C T G C AGAG C T G T AC C AGAAAGAAG G T AT C C C AC T GAT T AT T T TAG C AG GAAAGAAAT AT G G T T C AG G AAACTCCAGAGACTGGGCTGCCAAAGGACCGTATTTACTGGGTGTGAAAGCTGTTTTGGCCGAA AGT TAT GAAAAAATACACAAAGAT CAT T T GAT TGGAAT T GGCATAGC T CCAC T T CAGT T CC T T C CAGGAGAAAATGCAGATTCCTTGGGCCTCTCCGGTAGAGAAACATTTTCTTTAACATTTCCTGA AGAAC TGTCTCCTG GAAT T AC AT T GAAT AT AC AGAC AAG C AC T G GAAAAG T AT T C AG C G T GAT T GCTTCGTTT GAAGAT GAT G T G GAAAT AAC AT TAT AC AAAC AT G GAG GAT TAT T AAAC T T T G T G G CAC GAAAAT TCTCA

Ready-to-use lentiviral particle of iron-responsive element binding protein 2 (IREB2) in pLent-SV40-Puro-CMV-FH, with C terminal Myc and Flag.

ATGGACGCCCCAAAAGCAGGATACGCCTTTGAGTACCTTATTGAAACATTAAATGACAG TTCACATAAGAAGTTCTTCGATGTATCTAAACTTGGCACCAAGTATGATGTTCTGCCTTACTCA ATACGGGTCTTGTTGGAAGCTGCTGTACGAAATTGTGATGGCTTTTTAATGAAGAAGGAAGATG TTATGAACATTTTAGACTGGAAAACCAAACAAAGCAATGTTGAAGTGCCCTTTTTCCCTGCCCG TGTTCTTCTTCAAGATTTTACTGGAATACCAGCAATGGTGGATTTTGCTGCTATGAGGGAGGCA GTGAAAACTCTTGGAGGTGATCCTGAGAAAGTCCATCCTGCTTGTCCGACAGATCTTACAGTTG ACCATTCTTTACAAATTGACTTCAGTAAATGTGCAATACAGAATGCACCAAATCCTGGAGGTGG TGACCTGCAGAAAGCAGGAAAGCTCTCTCCACTTAAAGTGCAGCCTAAGAAGCTTCCCTGCAGA GGCCAGACTACCTGCCGAGGATCTTGTGATTCTGGAGAACTAGGCCGAAACTCAGGAACATTTT CTTCGCAGATTGAGAATACACCCATCCTGTGTCCTTTTCATTTGCAACCAGTGCCTGAACCTGA AACAGTGTTAAAAAATCAAGAAGTAGAATTCGGCAGAAATCGAGAGAGGCTTCAGTTTTTTAAG TGGAGTTCAAGAGTTTTTAAGAATGTGGCAGTGATCCCTCCTGGAACTGGAATGGCTCATCAAA TAAACTTAGAATATTTGTCAAGAGTGGTTTTTGAAGAAAAAGACCTCCTCTTCCCAGACAGTGT AGTCGGCACAGATTCACACATAACGATGGTGAATGGTTTAGGGATTCTGGGGTGGGGGGTTGGA GGCATTGAAACAGAAGCAGTTATGCTTGGTCTGCCAGTTTCTCTTACTTTACCAGAGGTGGTTG GATGTGAGTTAACTGGGTCATCAAACCCTTTTGTTACATCCATAGATGTTGTTCTTGGTATTAC AAAGCACCTCAGGCAAGTAGGAGTGGCTGGAAAGTTTGTTGAGTTTTTTGGAAGTGGAGTTTCA CAATTATCTATAGTTGATCGAACTACAATAGCAAACATGTGTCCGGAATATGGTGCTATCCTCA GCTTTTTCCCTGTTGACAATGTGACATTAAAACATTTAGAACATACAGGTTTTAGCAAAGCCAA ACTCGAATCAATGGAAACATACCTTAAAGCTGTGAAATTGTTTCGAAATGACCAGAATTCTTCA GGAGAACCTGAATACTCCCAGGTGATCCAGATTAATCTGAATTCAATAGTTCCATCTGTTAGTG GTCCAAAAAGACCTCAGGATAGAGTTGCTGTGACAGATATGAAAAGCGATTTCCAGGCTTGCTT AAATGAAAAGGTTGGATTTAAAGGCTTCCAAATTGCAGCTGAAAAACAAAAGGATATTGTCTCC ATTCATTATGAAGGAAGTGAATATAAGCTGTCTCATGGATCAGTGGTCATTGCTGCAGTTATCA GTTGTACCAATAATTGCAATCCATCTGTCATGCTTGCTGCAGGTCTTTTGGCTAAAAAGGCTGT TGAAGCTGGTCTGCGTGTTAAACCTTATATAAGAACAAGTTTATCTCCAGGCAGTGGGATGGTT ACACATTACCTCAGTTCAAGTGGAGTATTACCATATCTAAGTAAGCTTGGATTTGAAATCGTTG GCTATGGATGTTCAACTTGTGTGGGAAATACAGCACCCTTATCAGACGCAGTTTTAAATGCAGT AAAACAGGGTGATTTGGTTACCTGTGGAATTTTATCTGGAAACAAAAATTTTGAAGGTCGTCTT TGTGATTGTGTTCGTGCCAATTATCTTGCCTCTCCACCCTTAGTGGTAGCTTATGCCATAGCAG GCACAGTGAATATAGATTTCCAGACAGAACCTTTAGGTACTGACCCCACCGGCAAGAACATTTA CCTGCATGATATTTGGCCTAGTCGAGAAGAAGTTCATCGAGTAGAGGAAGAACATGTTATACTA TCCATGTTTAAAGCATTAAAAGATAAAATAGAAATGGGGAATAAACGGTGGAATTCCTTAGAAG CACCGGATTCAGTTTTGTTTCCATGGGACTTAAAGTCTACTTATATCAGATGCCCTTCATTTTT TGATAAACTTACCAAAGAGCCAATTGCACTCCAGGCTATTGAAAATGCCCATGTCTTATTATAT TTGGGAGACTCTGTCACAACAGATCATATATCACCTGCAGGAAGTATCGCTAGGAATAGTGCTG CCGCTAAGTATTTGACAAACAGAGGCCTTACCCCTCGTGAATTCAACTCTTACGGAGCTCGAAG AGGTAATGATGCTGTAATGACAAGAGGCACTTTTGCAAATATCAAGCTTTTTAATAAGTTTATT GGAAAACCAGCTCCTAAAACAATTCATTTTCCATCAGGACAGACGCTAGATGTATTTGAGGCTG CAGAGCTGTACCAGAAAGAAGGTATCCCACTGATTATTTTAGCAGGAAAGAAATATGGTTCAGG AAACTCCAGAGACTGGGCTGCCAAAGGACCGTATTTACTGGGTGTGAAAGCTGTTTTGGCCGAA AGTTATGAAAAAATACACAAAGATCATTTGATTGGAATTGGCATAGCTCCACTTCAGTTCCTTC CAGGAGAAAATGCAGATTCCTTGGGCCTCTCCGGTAGAGAAACATTTTCTTTAACATTTCCTGA AGAACTGTCTCCTGGAATTACATTGAATATACAGACAAGCACTGGAAAAGTATTCAGCGTGATT GCTTCGTTTGAAGATGATGTGGAAATAACATTATACAAACATGGAGGATTATTAAACTTTGTGG CACGAAAATTCTCA

UNC45A

Premade Adenovirus with ORF of unc-45 homolog A (C. elegans) (UNC45A) , transcript variant 3 with C terminal Flag and His tag

CGCCATGACTGCCAGCTCAGTGGAGCAGCTGCGGAAGGAGGGCAATGAGCTGTTCAAAT GTGGAGACTACGGGGGCGCCCTGGCGGCCTACACTCAGGCCCTGGGTCTGGACGCGACGCCCCA GGACCAGGCCGTTCTGCACCGGAACCGGGCCGCCTGCCACCTCAAGCTGGAAGATTACGACAAA GCAGAAACAGAGGCATCCAAAGCCATTGAAAAGGATGGTGGGGATGTCAAAGCACTCTACCGGC GGAGCCAAGCCCTAGAGAAGCTGGGCCGCCTGGACCAGGCTGTCCTTGACCTGCAGAGATGTGT GAGCTTGGAGCCCAAGAACAAAGTTTTCcaggaggccttgcGGAACATCGGGGGCCAGATTCAG GAGAAGGTGCGATACATGTCCTCGACGGATGCCAAAGTGGAACAGATGTTTCAGATACTG11gg acccagaagaGAAGGGCACTGAGAAAAAGCAAAAGGCTTCTCAGAACCTGGTGGTGCTggccag ggaggatgCTGGAGCGGAGAAGATCTTCCGGAGTAATGGGGTTCAGCTCTTGCAACGTTTACTG GACATGGGAGAGactgacctcatgcTGGCGGCTCTGCGTACGCTGGTTGGCATTTGCTCTGAGC ATCAGTCACGGACAGTGGCAACCCTGAGCATACTGGGAACTCGGCGAGTAGTCTCCATCCTGGG CGTGGAAAGCCAGGCTGTGTCCCTGGCTGCCTGCCACCTGCTGCAGGTTATGTTTGATGCCCTC AAGGAAGGTGTCAAAAAAGGCTTCCGAGGCAAAGAAGGTGCCATCATTGTGGATCCTGCCCGGG AGCTGAAGGTCCTCATCAGTAACCTCTTAGATCTGCTGACAGAGGTGGGGGTCTCTGGCCAAGG CCGAGACAATGCCCTGACCCTCCTGATTAAAGCGGTGCCCCGGAAGTCTCTCAAGGACCCCAAC AACAGCCTCACCCTCTGGGTCATCGACCAAGGTCTGAAAAAGATTTTGgaagtggggggctctc tACAGGACCCTCCTGGGGAGCTCGCAGTGACCGCAAACAGCCGCATGAGCGCCTCTATTCTCCT CAGCAAGCTCTTTGATGACCTCAAGTGTGATGCGGAGAGGGAGAATTTCCACAGACTTTGTGAA AACTACATCAAGAGCTGGTTTGAGGGCCAAGGGCTGGCCGGGAAGCTACGGGCCATCCAGACGG TGTCCTGCCTCCTGCAGGGCCCATGTGACGCTGGCAACCGGGCCTTGGAGCTGAGCGGTGTCAT GGAGAGTGTGATTGCTCTGTGTGCCTCTGAGCAGGAGGAGGAGCAGCTGGTGGCCGTGGAGGCT CTGATCCATGCAGCCGGCAAGGCTAAGCGGGCCTCATTCATCACTGCCAATGGTGTCTCGCTGC TGAAGGACCTATATAAGTGCAGCGAGAAGGACAGCATCCGCATCCGGGCGCTAGTGGGACTCTG TAAGCTCGGTTCGGCTGGAGGGACTGACTTCAGCATGAAGCAGTTTGCTGAAGGCTCCACTCTC AAACTGGCTAAGCAGTGTCGAAAGTGGCTGTGCAATGACCAGATCGACGCAGGCACTCGGCGCT GGGCAGTGGAGGGCCTGGCTTACCTGACCTTTGATGCCGACGTGAAGGAAGAGTTTGTGGAGGA TGCGGCTGCTCTGAAAGCTCTGTTCCAGCTCAGCAGGTTGGAGGAGAGGTCAGTGCTCTTTGCG GTGGCCTCAGCGCTGGTGAACTGCACCAACAGCTATGACTACGAGGAGCCCGACCCCAAGATGG TGGAGCTGGCCAAGTATGCCAAGCAGCATGTGCCCGAGCAGCACCCCAAGGACAAGCCAAGCTT CGTGCGGGCTCGGGTGAAGAAGCTGCTGGCAGCGGGTGTGGTGTCGGCCATGGTGTGCATGGTG AAGACGGAGAGCCCTGTGCTGACCAGTTCCTGCAGAGAGCTGCTCTCCAGGGTCTTCTTGGCTT TAGTGGAAGAGGTAGAGGaccgaggcactgtGGTTGCCCAGGGAGGCGGCAGGGCGCTGATCCC GCTGGCCCtggaaggcacggaCGTGGGGCAGACAAAGGCAGCCCAGGCCCTTGCCAAGCTCACC ATCACCTCCAACCCGGAGATGACCTTCCCTGGCGAGCGGATCTATGAGGTGGTCCGGCCCCTCG TCTCCCTGTTGCACCTCAACTgctcaggcctgcaGAACTTCGAGGCGCTCATGGCCCTAACAAA CCTGGCTGGGATCAGCGAGAGGCTCCGGCAGAAGATCCTGAAGgagaaggctgtgcCCATGATA GAAGGCTACATGTTTGAGGAGCATGAGATGATCCGCCGGGCAGCCACGGAGTGCATGTGTAACT TGGCCATGAGCAAGGAGGTGCAGGACCTCTTcgaagcccagggcaATGACCGACTGAAGCTGCT GGTGCTGTACAGTGGAGAGGATGATGAGCTGCTACAGCGGGCAGCTGCCGGGGGCTTGGCCATG CTTACCTCCATGCGGCCCACGCTCTGCAGCCGCATTCCCCAAGTGACCACACACTGGCTGGAGA TCCTGCAGGCCCTGCTTCTGAGCTCCAACCAGGAGCTGCAGCACCGGGGTGCTGTGGTGGTGCT GAACATGGTGGAGGCCTCGAGGGAGATTGCCAGCACCCTGATGGAGAGTGAGATGATGGAGATC TTGTCAGTGCTAGCTAAGGGTGACCACAGCCCTGTcacaagggctgctgCAGCCTGCCTGGACA AAGCAGTGGAATATGGGCTTATCCAACCCAACCAAgatggagaga

Premade Adenovirus with ORF of unc-45 homolog A (C. elegans) (UNC45A) , transcript variant 2 with C terminal Flag and His tag.

Ready-to-use lentiviral particle of unc-45 homolog A (C. elegans) (UNC45A) , transcript variant 2 in pLent-SV40-Puro-CMV- FH, with C terminal Myc and Flag.

CGCCATGACTGTGAGTGGTCCAGGGACCCCCGAGCCCCGGCCGGCCACCCCCGGGGCCA GCTCAGTGGAGCAGCTGCGGAAGGAGGGCAATGAGCTGTTCAAATGTGGAGACTACGGGGGCGC CCTGGCGGCCTACACTCAGGCCCTGGGTCTGGACGCGACGCCCCAGGACCAGGCCGTTCTGCAC CGGAACCGGGCCGCCTGCCACCTCAAGCTGGAAGATTACGACAAAGCAGAAACAGAGGCATCCA AAGCCATTGAAAAGGATGGTGGGGATGTCAAAGCACTCTACCGGCGGAGCCAAGCCCTAGAGAA GCTGGGCCGCCTGGACCAGGCTGTCCTTGACCTGCAGAGATGTGTGAGCTTGGAGCCCAAGAAC AAAGTTTTCCAGGAGGCCTTGCGGAACATCGGGGGCCAGATTCAGGAGAAGGTGCGATACATGT CCTCGACGGATGCCAAAGTGGAACAGATGTTTCAGATACTGTTGGACCCAGAAGAGAAGGGCAC TGAGAAAAAGCAAAAGGCTTCTCAGAACCTGGTGGTGCTGGCCAGGGAGGATGCTGGAGCGGAG AAGATCTTCCGGAGTAATGGGGTTCAGCTCTTGCAACGTTTACTCGACATGGGAGAGACTGACC TCATGCTGGCGGCTCTGCGTACGCTGGTTGGCATTTGCTCTGAGCATCAGTCACGGACAGTGGC AACCCTGAGCATACTGGGAACTCGGCGAGTAGTCTCCATCCTGGGCGTGGAAAGCCAGGCTGTG TCCCTGGCTGCCTGCCACCTGCTGCAGGTTATGTTTGATGCCCTCAAGGAAGGTGTCAAAAAAG GCTTCCGAGGCAAAGAAGGTGCCATCATTGTGGATCCTGCCCGGGAGCTGAAGGTCCTCATCAG TAACCTCTTAGATCTGCTGACAGAGGTGGGGGTCTCTGGCCAAGGCCGAGACAATGCCCTGACC CTCCTGATTAAAGCGGTGCCCCGGAAGTCTCTCAAGGACCCCAACAACAGCCTCACCCTCTGGG TCATCGACCAAGGTCTGAAAAAGATTTTGGAAGTGGGGGGCTCTCTACAGGACCCTCCTGGGGA GCTCGCAGTGACCGCAAACAGCCGCATGAGCGCCTCTATTCTCCTCAGCAAGCTCTTTGATGAC CTCAAGTGTGATGCGGAGAGGGAGAATTTCCACAGACTTTGTGAAAACTACATCAAGAGCTGGT TTGAGGGCCAAGGGCTGGCCGGGAAGCTACGGGCCATCCAGACGGTGTCCTGCCTCCTGCAGGG CCCATGTGACGCTGGCAACCGGGCCTTGGAGCTGAGCGGTGTCATGGAGAGTGTGATTGCTCTG TGTGCCTCTGAGCAGGAGGAGGAGCAGCTGGTGGCCGTGGAGGCTCTGATCCATGCAGCCGGCA AGGCTAAGCGGGCCTCATTCATCACTGCCAATGGTGTCTCGCTGCTGAAGGACCTATATAAGTG CAGCGAGAAGGACAGCATCCGCATCCGGGCGCTAGTGGGACTCTGTAAGCTCGGTTCGGCTGGA GGGACTGACTTCAGCATGAAGCAGTTTGCTGAAGGCTCCACTCTCAAACTGGCTAAGCAGTGTC GAAAGTGGCTGTGCAATGACCAGATCGACGCAGGCACTCGGCGCTGGGCAGTGGAGGGCCTGGC TTACCTGACCTTTGATGCCGACGTGAAGGAAGAGTTTGTGGAGGATGCGGCTGCTCTGAAAGCT CTGTTCCAGCTCAGCAGGTTGGAGGAGAGGTCAGTGCTCTTTGCGGTGGCCTCAGCGCTGGTGA ACTGCACCAACAGCTATGACTACGAGGAGCCCGACCCCAAGATGGTGGAGCTGGCCAAGTATGC CAAGCAGCATGTGCCCGAGCAGCACCCCAAGGACAAGCCAAGCTTCGTGCGGGCTCGGGTGAAG AAGCTGCTGGCAGCGGGTGTGGTGTCGGCCATGGTGTGCATGGTGAAGACGGAGAGCCCTGTGC TGACCAGTTCCTGCAGAGAGCTGCTCTCCAGGGTCTTCTTGGCTTTAGTGGAAGAGGTAGAGGA CCGAGGCACTGTGGTTGCCCAGGGAGGCGGCAGGGCGCTGATCCCGCTGGCCCTGGAAGGCACG GACGTGGGGCAGACAAAGGCAGCCCAGGCCCTTGCCAAGCTCACCATCACCTCCAACCCGGAGA TGACCTTCCCTGGCGAGCGGATCTATGAGGTGGTCCGGCCCCTCGTCTCCCTGTTGCACCTCAA CTGCTCAGGCCTGCAGAACTTCGAGGCGCTCATGGCCCTAACAAACCTGGCTGGGATCAGCGAG AGGCTCCGGCAGAAGATCCTGAAGGAGAAGGCTGTGCCCATGATAGAAGGCTACATGTTTGAGG AGCATGAGATGATCCGCCGGGCAGCCACGGAGTGCATGTGTAACTTGGCCATGAGCAAGGAGGT GCAGGACCTCTTCGAAGCCCAGGGCAATGACCGACTGAAGCTGCTGGTGCTGTACAGTGGAGAG GATGATGAGCTGCTACAGCGGGCAGCTGCCGGGGGCTTGGCCATGCTTACCTCCATGCGGCCCA CGCTCTGCAGCCGCATTCCCCAAGTGACCACACACTGGCTGGAGATCCTGCAGGCCCTGCTTCT GAGCTCCAACCAGGAGCTGCAGCACCGGGGTGCTGTGGTGGTGCTGAACATGGTGGAGGCCTCG AGGGAGATTGCCAGCACCCTGATGGAGAGTGAGATGATGGAGATCTTGTCAGTGCTAGCTAAGG GTGACCACAGCCCTGTCACAAGGGCTGCTGCAGCCTGCCTGGACAAAGCAGTGGAATATGGGCT TATCCAACCCAACCAAGATGGagaga

VPS33B

Premade Adenovirus with ORF of vacuolar protein sorting 33 homolog B (yeast) (VPS33B) with C terminal Flag and His tag

CGCCATGGCTTTTCCCCATCGGCCGGACGCCCCTGAGCTGCCTGACTTCTCCATGCTGA AGAGGCTGGCTCGAGACCAGCTCATCTATCTGCTGGAGCAGCTTCCTGGAAAAAAGGATTTATT CATTGAGGCAGATCTCatgagccctttggaTCGAATTGCCAATGTCTCCATCCTGAAGCAACAC GAAGTAGACAAGCTATACAAGGTGGAGAACAAGCCAGCCCTCAGCTCCAATGAACAATTGTGCT TCTTGGTCAGACCCCGCATCAAGAATATGCGATACATTGCCAGTCTTGTCAATGCTGACAAATT GGCTGGCCGAACTCGCAAATACAAAGTGATCttcagccctcaaaaGTTCTATGCGTGTGAGATG GTGCTTGAGGAAGAGGGAATCTATGGAGATGTGAGCTGTGATGAATGGGCCTTCTCTTTGCTGC CTCTTGATGTGGATCTGCTGAGCATGGAACTACCAGAATTTTTCAGGGATTACTTTCTGGAAGG AGATCAGCGTTGGATCAACACTGTAGCTCAGGCCTTACACCTTCTCAGCACTCTCTatggaccc tttccaAACTGCTATGGAATTGGCAGGTGCGCCAAGATGGCATATGAATTGTGGAGGAACCTGG AGGAGGAGGAGGATGGCGAAACCAAGGGCCGAAGGCCAGAGATTGGACATATCTTTCTCTTGGA CAGAGATGTGGACTTTGTGACAGCACTTTGCTCCCAAGTGGTTtatgagggcctagtAGATGAC ACCTTCCGCATCAAGTGTGGGAGTGTCGACTTTGGCCCAGAAGTCACATCCTCTGACAAGAGCC TGAAGGTGCTACTCAATGCCGAGGACAAGGTGTTTAATGAGATTCGGAACGAGCACTTCTCCAA TGTCTTTGGCTTCTTGAGCCAGAAGGCCCGGAACTTGCAGGCCCAGTATGATCGCCGGAGAGGC ATGGACATTAAGCAGATGAAGAATTTCGTGTCCCAGGAGCTCAAGGGCCTGAAACAGGAGCACC GCCTGCTGAGTCTCCATATTGGGGCCTGTGAATCCATCATGAAGAAGAAAACCAAGCAGGATTT CCAGGAGCTAATCAAGACTGAGCATGCACTGCTAGAGGGGTTCAACATCCGGGAGAGCACCAGC TACATTGAGGAACACATAGACCGGCAGGTGTCGCCTATAGAAAGCCTGCGCCTCATGTGCCTTT TGTCCATCACTGAGAATGGTTTGATCCCCAAGGATTACCGATCTCTGAAAACACAGTATCTGCA GAGCTATGGCCCTGAGCACCTGCTAACCTTCTCCAATCTGCGAAGAGCTGGGCTCCTAACGGAG CAGGCCCCCGGGGACACCCTCACAGCCGTGGAGAGTAAAGTGAGCAAGCTGGTGACCGACAAGG CTGCAGGAAAGATTACTGATGCCTTCAGTTCTCTGGCCAAGAGGAGCAATTTTCGTGCCATCAG CAAAAAGCTGAATTTGATCCCACGTGTGGACGGCGAGTATGATCTGAAAGTGCCCCGAGACATG GCTTACGTCTTCAGTGGTGCTTATGTGCCCCTGAGCTGCCGAATCATTGAGCAGGTGCTAGAGC GGCGAAGCTGGcagggccttgatgAGGTGGTACGGCTGCTCAACTGCAGTGACTTTGCATTCAC AGATATGACTAAGGAAGACAAGGCTTCCAGTGAGTCCCTGCGCCTCATCTTGGTGGTGTTCTTG

GGTGGTTGTACATTCTCTGAGATctcagccctccggtTCCTGGGCAGAGAGAAAGGCTACAGGT

TCATTTTCCTGACGACAGCAGTCACAAACAGCGCTCGCCTTATGGAGGCCATGAGTGaggtgaa agcca

Ready-to-use lentiviral particle of vacuolar protein sorting 33 homolog B (yeast) (VPS33B) in pLent-SV40-Puro-CMV-FH, with C terminal Myc and Flag.

CGCCATGGCTTTTCCCCATCGGCCGGACGCCCCTGAGCTGCCTGACTTCTCCATGCTGA AGAGGCTGGCTCGAGACCAGCTCATCTATCTGCTGGAGCAGCTTCCTGGAAAAAAGGATTTATT CATTGAGGCAGATCTCatgagccctttggaTCGAATTGCCAATGTCTCCATCCTGAAGCAACAC GAAGTAGACAAGCTATACAAGGTGGAGAACAAGCCAGCCCTCAGCTCCAATGAACAATTGTGCT TCTTGGTCAGACCCCGCATCAAGAATATGCGATACATTGCCAGTCTTGTCAATGCTGACAAATT GGCTGGCCGAACTCGCAAATACAAAGTGATCttcagccctcaaaaGTTCTATGCGTGTGAGATG GTGCTTGAGGAAGAGGGAATCTATGGAGATGTGAGCTGTGATGAATGGGCCTTCTCTTTGCTGC CTCTTGATGTGGATCTGCTGAGCATGGAACTACCAGAATTTTTCAGGGATTACTTTCTGGAAGG AGATCAGCGTTGGATCAACACTGTAGCTCAGGCCTTACACCTTCTCAGCACTCTCTatggaccc tttccaAACTGCTATGGAATTGGCAGGTGCGCCAAGATGGCATATGAATTGTGGAGGAACCTGG AGGAGGAGGAGGATGGCGAAACCAAGGGCCGAAGGCCAGAGATTGGACATATCTTTCTCTTGGA CAGAGATGTGGACTTTGTGACAGCACTTTGCTCCCAAGTGGTTtatgagggcctagtAGATGAC ACCTTCCGCATCAAGTGTGGGAGTGTCGACTTTGGCCCAGAAGTCACATCCTCTGACAAGAGCC TGAAGGTGCTACTCAATGCCGAGGACAAGGTGTTTAATGAGATTCGGAACGAGCACTTCTCCAA TGTCTTTGGCTTCTTGAGCCAGAAGGCCCGGAACTTGCAGGCCCAGTATGATCGCCGGAGAGGC ATGGACATTAAGCAGATGAAGAATTTCGTGTCCCAGGAGCTCAAGGGCCTGAAACAGGAGCACC GCCTGCTGAGTCTCCATATTGGGGCCTGTGAATCCATCATGAAGAAGAAAACCAAGCAGGATTT CCAGGAGCTAATCAAGACTGAGCATGCACTGCTAGAGGGGTTCAACATCCGGGAGAGCACCAGC TACATTGAGGAACACATAGACCGGCAGGTGTCGCCTATAGAAAGCCTGCGCCTCATGTGCCTTT TGTCCATCACTGAGAATGGTTTGATCCCCAAGGATTACCGATCTCTGAAAACACAGTATCTGCA GAGCTATGGCCCTGAGCACCTGCTAACCTTCTCCAATCTGCGAAGAGCTGGGCTCCTAACGGAG CAGGCCCCCGGGGACACCCTCACAGCCGTGGAGAGTAAAGTGAGCAAGCTGGTGACCGACAAGG CTGCAGGAAAGATTACTGATGCCTTCAGTTCTCTGGCCAAGAGGAGCAATTTTCGTGCCATCAG CAAAAAGCTGAATTTGATCCCACGTGTGGACGGCGAGTATGATCTGAAAGTGCCCCGAGACATG GCTTACGTCTTCAGTGGTGCTTATGTGCCCCTGAGCTGCCGAATCATTGAGCAGGTGCTAGAGC GGCGAAGCTGGcagggccttgatgAGGTGGTACGGCTGCTCAACTGCAGTGACTTTGCATTCAC AGATATGACTAAGGAAGACAAGGCTTCCAGTGAGTCCCTGCGCCTCATCTTGGTGGTGTTCTTG GGTGGTTGTACATTCTCTGAGATctcagccctccggtTCCTGGGCAGAGAGAAAGGCTACAGGT TCATTTTCCTGACGACAGCAGTCACAAACAGCGCTCGCCTTATGGAGGCCATGAGTGaggtgaa agcca

PSMD3

Premade Adenovirus with ORF of proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 (PSMD3) with C terminal Flag and His tag.

CGCCATGAAGCAGGAGGGCTCGGCGCGGCGCCGCGGCGCGGACAAGGCGAAACCGCCGC CCGGCGGAGGAGAACAAGAACCCCCACCGCCGCCGGCCCCCCAGGATGTGGAGATGAAAGAGGA GGCAGCGACGGGTGGCGGGTCGACGGGGGAGGCAGACGGCAAGACGGCGGCGGCAGCGGCTGAG CACTCCCAGCGAGAGCTGGACACAGTCACCTTGGAGGACATCAAGGAGCACGTGAAACAGCTAG AGAAAGCGGTTTCAGGCAAGGAGCCGAGATTCGTGCTGCGGGCCCTGCGGATGCTGCCTTCCAC ATCACGCCGCCTCAACCACTATGTTCTGTATAAGGCTGTGCAGGGCTTCTTCACTTCAAATAAT GCCACTCGAGACTTTTTGCTCCCCTTCCTGGAAGAGCCCATGGACACAGAGGCTGATTTACAGT TCCGTCCCCGCACGGGAAAAGCTGCGTCGACACCCCTCCTGCCTGAAGTGGAAGCCTATCTCCA ACTCCTCGTGGTCATCTTCATGATGAACAGCAAGCGCTACAAAGAGGCACAGAAGATCTCTGAT GATCTGATGCAGAAGATCAGTACTCAGAACCGCCGGGCCCTAGACCTTGTAGCCGCAAAGTGTT ACTATTATCACGCCCGGGTCTATGAGTTCCTGGACAAGCTGGATGTGGTGCGCAGCTTCTTGCA TGCTCGGCTCCGGACAGCTACGCTTCGGCATGACGCAGACGGGCAGGCCACCCTGTTGAACCTC CTGCTGCGGAATTACCTACACTACAGCTTGTACGACCAGGCTGAGAAGCTGGTGTCCAAGTCTG TGTTCCCAGAGCAGGCCAACAACAATGAGTGGGCCAGGTACCTCTACTACACAGGGCGAATCAA AGCCATCCAGCTGGAGTACTCAGAGGCCCGGAGAACGATGACCAACGCCCTTCGCAAGGCCCCT CAGCACACAGCTGTCGGCTTCAAACAGACGGTGCACAAGCTTCTCATCGTGGTGGAGCTGTTGC TGGGGGAGATCCCTGACCGGCTGCAGTTCCGCCAGCCCTCCCTCAAGCGCTCACTCATGCCCTA TTTCCTTCTGACTCAAGCTGTCAGGACAGGAAACCTAGCCAAGTTCAACCAGGTCCTGGATCAG TTTGGGGAGAAGTTTCAAGCAGATGGGACCTACACCCTAATTATCCGGCTGCGGCACAACGTGA TTAAGACAGGTGTACGCATGATCAGCCTCTCCTATTCCCGAATCTCCTTGGCTGACATCGCCCA GAAGCTGCAGTTGGATAGCCCCGAAGATGCAGAGTTCATTGTTGCCAAGGCCATCCGGGATGGT GTCATTGAGGCCAGCATCAACCACGAGAAGGGCTATGTCCAATCCAAGGAGATGATTGACATCT ATTCCACCCGAGAGCCCCAGCTAGCCTTCCACCAGCGCATCTCCTTCTGCCTAGATATCCACAA CATGTCTGTCAAGGCCATGAGGTTTCCTCCCAAATCGTACAACAAGGACTTGGAGTCTGCAGAG GAACGGCGTGAGCGAGAACAGCAGGACTTGGAGTTTGCCAAGGAGATGGCAGAAGATGATGATG ACAGCTTCCCTa Ready-to-use lentiviral particle of proteasome (prosome, macropain) 26S subunit, non-ATPase, 3 (PSMD3) in pLent-SV40-Puro- CMV-FH, with C terminal Myc and Flag.

CGCCATGAAGCAGGAGGGCTCGGCGCGGCGCCGCGGCGCGGACAAGGCGAAACCGCCGC CCGGCGGAGGAGAACAAGAACCCCCACCGCCGCCGGCCCCCCAGGATGTGGAGATGAAAGAGGA GGCAGCGACGGGTGGCGGGTCGACGGGGGAGGCAGACGGCAAGACGGCGGCGGCAGCGGCTGAG CACTCCCAGCGAGAGCTGGACACAGTCACCTTGGAGGACATCAAGGAGCACGTGAAACAGCTAG AGAAAGCGGTTTCAGGCAAGGAGCCGAGATTCGTGCTGCGGGCCCTGCGGATGCTGCCTTCCAC ATCACGCCGCCTCAACCACTATGTTCTGTATAAGGCTGTGCAGGGCTTCTTCACTTCAAATAAT GCCACTCGAGACTTTTTGCTCCCCTTCCTGGAAGAGCCCATGGACACAGAGGCTGATTTACAGT TCCGTCCCCGCACGGGAAAAGCTGCGTCGACACCCCTCCTGCCTGAAGTGGAAGCCTATCTCCA ACTCCTCGTGGTCATCTTCATGATGAACAGCAAGCGCTACAAAGAGGCACAGAAGATCTCTGAT GATCTGATGCAGAAGATCAGTACTCAGAACCGCCGGGCCCTAGACCTTGTAGCCGCAAAGTGTT ACTATTATCACGCCCGGGTCTATGAGTTCCTGGACAAGCTGGATGTGGTGCGCAGCTTCTTGCA TGCTCGGCTCCGGACAGCTACGCTTCGGCATGACGCAGACGGGCAGGCCACCCTGTTGAACCTC CTGCTGCGGAATTACCTACACTACAGCTTGTACGACCAGGCTGAGAAGCTGGTGTCCAAGTCTG TGTTCCCAGAGCAGGCCAACAACAATGAGTGGGCCAGGTACCTCTACTACACAGGGCGAATCAA AGCCATCCAGCTGGAGTACTCAGAGGCCCGGAGAACGATGACCAACGCCCTTCGCAAGGCCCCT CAGCACACAGCTGTCGGCTTCAAACAGACGGTGCACAAGCTTCTCATCGTGGTGGAGCTGTTGC TGGGGGAGATCCCTGACCGGCTGCAGTTCCGCCAGCCCTCCCTCAAGCGCTCACTCATGCCCTA TTTCCTTCTGACTCAAGCTGTCAGGACAGGAAACCTAGCCAAGTTCAACCAGGTCCTGGATCAG TTTGGGGAGAAGTTTCAAGCAGATGGGACCTACACCCTAATTATCCGGCTGCGGCACAACGTGA TTAAGACAGGTGTACGCATGATCAGCCTCTCCTATTCCCGAATCTCCTTGGCTGACATCGCCCA GAAGCTGCAGTTGGATAGCCCCGAAGATGCAGAGTTCATTGTTGCCAAGGCCATCCGGGATGGT GTCATTGAGGCCAGCATCAACCACGAGAAGGGCTATGTCCAATCCAAGGAGATGATTGACATCT ATTCCACCCGAGAGCCCCAGCTAGCCTTCCACCAGCGCATCTCCTTCTGCCTAGATATCCACAA CATGTCTGTCAAGGCCATGAGGTTTCCTCCCAAATCGTACAACAAGGACTTGGAGTCTGCAGAG GAACGGCGTGAGCGAGAACAGCAGGACTTGGAGTTTGCCAAGGAGATGGCAGAAGATGATGATG ACAGCTTCCCTa

TUBB1

Premade Adenovirus with ORF of tubulin, beta 1 ( TUBB1 ) with C terminal Flag and His tag.

CGCCATGCGTGAAATTGTCCATATTCAGATTGGCCAGTGTGGCAACCAGATCGGAGCCA AGTTCTGGGAGATGATTGGTGAGGAACACGGGATCGACTTGGCTGGGAGCGACCGCGGGGCCTC GGCCTTGCAGCTGGAGAGAATCAGCGTGTACTACAACGAAGCCTACGGTAGGAAATATGTGCCC CGAGCAGTCTTGGTGGACCTAGAACCTGGGACGATGGACAGCATTCGATCTAGCAAATTAGGAG CTCTCTTTCAACCCGACAGTTTTGTCCATGGTAACTCTGGGGCTGGCAACAACTGGGCCAAAGG CCACTACACGGAGGGAGCCGAGCTGATCGAGAATGTCCTAGAGGTGGTGAGGCACGAGAGTGAG AGCTGTGACTGCCTGCAGGGCTTCCAGATCGTCCACTCCCTGGGCGGGGGCACAGgctccggga tgggcACTCTGCTCATGAACAAGATTAGAGAGGAGTACCCGGACCGGATCATGAATTCCTTCAG CGTCATGCCTTCTCCCAAGGTGTCGGACACGGTGGTGGAGCCCTACAACGCGGTTCTGTCTATC CACCAGCTGATTGAGAATGCAGATGCCTGTTTCTGCATTGACAATGAGGCCCTCTATGACATCT GCTTCCGTACCCTGAAGCTGACGACACCCACCTATGGGGATCTCAACCACCTAGTGTCCTTGAC CATGAGCGGCATAACCACCTCCCTCCGGTTCCCGGGTCAGCTCAACGCAGACCTGCGCAAGCTG GCGGTGAACATGGTCCCCTTCCCCCGCCTGCACTTCTTTATGCCCGGCTTTGCCCCACTCACGg cccagggcagccaGCAGTACCGAGCCCTCTCCGTGGCCGAGCTCACCCAGCAGATGTTCGATGC CCGCAATaccatggctgcctGTGACCTCCGCCGTGGCCGCTACCTCACAGTGGCCTGCATTTTC CGGGGCAAGATGTCCACCAAGGAAGTGGACCAGCAACTGCTCTCCGTGCAGACCAGGAACAGCA GCTGCTTTGTGGAGTGGATTCCCAACAACGTCAAGGTGGCTGTCTGCGACATCCCGCCCCGGGG GCTGAGCATGGCCGCCACCTTCATTGGCAACAACACGGCCATCCAAGAGATCTTTAATAGGGTC TCTGAGCATTTCTCAGCCATGTTCAAAAGGAAAGCTTTTGTGCACTGGTACACCAGCGAAGGGA TGGACATAAACGAATTTGGGGAAGCTGAAAATAACATCCATGATTTGGTATCCGAGTACCAACA ATTTCAAGATGCCAAAGCAGTTCTAGAGGAAGATGAAGAGGTCACGGAGGAGGCAGAAATGGAG CCAGAAGataagggacata

Premade Adenovirus with ORF of tubulin, beta (TUBB) with C terminal Flag and His tag.

CGCCATGAGGGAAATCGTGCACATCCAGGCTGGTCAGTGTGGCAACCAGATCGGTGCCA AGTTCTGGGAGGTGATCAGTGATGAACATGGCATCGACCCCACCGGCACCTACCACGGGGACAG CGACCTGCAGCTGGACCGCATCTCTGTGTACTACAATGAAGCCACAGGTGGCAAATATGTTCCT CGTGCCATCCTGGTGGATCTAGAACCTGGGACCATGGACTCTGTTCGCTCAGGTCCTTTTGGCC AGATCTTTAGACCAGACAACTTTGTATTTGGTCAGTCTGGGGCAGGTAACAACTGGGCCAAAGG CCACTACACAGAGGGCGCCGAGCTGGTTGATTCTGTCCTGGATGTGGTACGGAAGGAGGCAGAG AGCTGTGACTGCCTGCAGGGCTTCCAGCTGACCCACTCACTGGGCGGGGGCACAGGCTCTGGAA TGGGCACTCTCCTTATCAGCAAGATCCGAGAAGAATACCCTGATCGCATCATGAATACCTTCAG TGTGGTGCCTTCACCCAAAGTGTCTGACACCGTGGTCGAGCCCTACAATGCCACCCTCTCCGTC CATCAGTTGGTAGAGAATACTGATGAGACCTATTGCATTGACAACGAGGCCCTCTATGATATCT GCTTCCGCACTCTGAAGCTGACCACACCAACCTACGGGGATCTGAACCACCTTGTCTCAGCCAC CATGAGTGGTGTCACCACCTGCCTCCGTTTCCCTGGCCAGCTCAATGCTGACCTCCGCAAGTTG GCAGTCAACATGGTCCCCTTCCCACGTCTCCATTTCTTTATGCCTGGCTTTGCCCCTCTCACCA GCCGTGGAAGCCAGCAGTATCGAGCTCTCACAGTGCCGGAACTCACCCAGCAGGTCTTCGATGC CAAGAACATGATGGCTGCCTGTGACCCCCGCCACGGCCGATACCTCACCGTGGCTGCTGTCTTC CGTGGTCGGATGTCCATGAAGGAGGTCGATGAGCAGATGCTTAACGTGCAGAACAAGAACAGCA GCTACTTTGTGGAATGGATCCCCAACAATGTCAAGACAGCCGTCTGTGACATCCCACCTCGTGG CCTCAAGATGGCAGTCACCTTCATTGGCAATAGCACAGCCATCCAGGAGCTCTTCAAGCGCATC TCGGAGCAGTTCACTGCCATGTTCCGCCGGAAGGCCTTCCTCCACTGGTACACAGGCGAGGGCA TGGACGAGATGGAGTTCACCGAGGCTGAGAGCAACATGAACGACCTCGTCTCTGAGTATCAGCA GTACCAGGATGCCACCGCAGAAGAGGAGGAGGATTTCGGTGAGGAGGCCGAAGAGGAGgcca

Ready-to-use lentiviral particle of tubulin, beta 1 (TUBB1) in pLent-SV40-Puro-CMV-FH, with C terminal Myc and Flag.

Ready-to-use lentiviral particle of tubulin, beta (TUBB) in pLent-SV4 O-Puro-CMV-FH, with C terminal Myc and Flag.

The items of this example are available for purchase, e.g. for research use at ViGene Biosciences Inc. Address: Suite 120, 9430 Key West Ave, Rockville, MD 20850 USA vigenebio.com

Example 6

Activation with recombinant AAV vectors

List of genes which expression should be increased or activated for therapeutic purposes (treatment and prophylaxis of aging, frailty and ARCD : PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3, TUBB1 (further any of it is Plus Gene, all of them are Plus Genes) Vectors can be acquired as shown in example or can be generated by triple transfection of HEK293 cells as described (Matsushita et al, 1998) . Cells were cultured in roller bottles

(Corning, New York, USA) in DMEM 10% FBS to 80% confluence and co-transfected with a plasmid carrying the expression cassette flanked by the AAV2 viral ITRs, a helper plasmid carrying the AAV rep2 and cap9 genes, and a plasmid carrying the adenovirus helper functions. The expression cassettes that can be used is (i) GFP under the control of CMV promoter and SV40 polyA signal or (ii) murine TRIM58 (or any other Plus Gene) under the control of CMV promoter (iii) murine catalytically inactive TRIM58 (or any other Plus Gene) under the control of CMV promoter (see Full Methods section for detailed description) . In AAV-TRIM58 (or any other Plus Gene) vectors, SV40 polyA should be used if 3' UTR from TRIM58 (or any other Plus Gene) is not maintained as a polyA signal. AAV vectors can be purified with an optimized method based on two consecutive cesium chloride gradients, dialyzed against PBS, filtered and stored at 808C until use (Ayuso et al, 2010) . The titers of viral genomes particles can be determined by quantitative real time PCR.

Example 7

Any of the recombinant proteins PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3, TUBB1 can be used as therapeutic agents for administration by humans or animals for therapeutic purposes (treatment and prophylaxis of aging, frailty and ARCD.

One of the methods of administration is IV injection 1,2,5 or 10 times a month, for 2,3 or 6 months, dosage is selected depending on the protein and the patient weight and condition.

Example 8

Prophetic examples of animal tests

Mice and animal procedures: Mice of pure C57/BL6 background can be produced and housed at the specific pathogen-free animal house by the methods known in the art. Mice aged from 10 to 15 months can be treated with the AAV9-TRIM58 (or any other Plus Gene) or AAV9-empty vector. Vectors can be administered via tail vein injection at a concentration of 3.5 3 1012 viral genomes per mouse . Gene therapy vector production: Viral vectors can be acquired ready for use or generated and purified as described previously. Vectors can be produced through triple transfection of HEK293T. Expression cassettes can be under the control of the cytomegalovirus promoter and can contain an SV40 polyA signal for EGFP and the cytomegalovirus promoter, and a specific region of the TRIM58 (or any other Plus Gene) gene as polyA signal for TRIM58 (or any other Plus Gene) . AAV9 particles can be purified using 2 cesium chloride gradients, dialyzed against phosphate buffered saline (PBS) and filtered. Viral genome particle titers can be determined by a quantitative real-time polymerase chain reaction (PCR) method. Treatment of 1- and 2-year old mice with an adeno associated virus (AAV), e.g. AAV9-TRIM58 (or any other Plus Gene )

will have beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging, (e.g. metilation age) The treated mice, both at 1-year and at 2-year of age, will have an increase in median lifespan and maximal lifespan.

The therapy can be administered by the methods known in the art 1, 2, 5 or 10 times a months for 1,3 or 5 cycles per year, dosage selected depending on the factors known in the

Claims

1. Method of treatment of at least one selected from the group: aging, frailty or aging related conditions and diseases (ARCD) comprising reduction or inhibition of protein selected from the group MACF1, OXCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1 in patient by therapeutic mean.

2. Method of claim 1 comprising administering an inhibitor of protein selected from the group MACF1, OXCT2P1, SLC12A7, CTC- 228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1, DHRS13, TUBB1 or pharmaceutical composition, comprising an inhibitor of such protein .

3. Method of claim 1, comprising administering an agent to reduce expression of a gene product encoded from at least one gene selected from the group MACF1 , OXCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1 , MAN2A2 , ERAL1, DHRS13, TUBB1.

4. Method of claim 3, wherein agent is siRNA, shRNA or other RNA.

5. Pharmaceutical composition, comprising an inhibitor of protein selected from the group MACF1 , OXCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1 , MAN2A2 , ERAL1, DHRS13, TUBB1.

6. Pharmaceutical composition of claim 4, wherein inhibitor is a small molecule, peptide, aptamer, protein, antibody or agent for protein degradation.

7. Pharmaceutical composition, comprising an agent to reduce expression of a gene product encoded from a gene encoding protein selected from the group MACF1 , OXCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1 , MAN2A2 , ERAL1, DHRS13, TUBB1.

8. Pharmaceutical composition of claim 7, wherein agent is a gene therapy .

9. Pharmaceutical composition of claim 7, wherein agent is siRNA, shRNA or other RNA.

10. Pharmaceutical composition, comprising an inhibitor of protein selected from the group MACF1 , OXCT2P1 , SLC12A7 , CTC-228N24.3, PSMA4 , RCCD1 , MAN2A2 , ERAL1, DHRS13, TUBB1 for the treatment of aging, frailty or ARCD.

11. A pharmaceutical composition comprising a gene therapy vector encoding gene selected from the group MACF1, OXCT2P1, SLC12A7, CTC-228N24.3, PSMA4 , RCCD1, MAN2A2 , ERAL1 , DHRS13, TUBB1 and a pharmaceutically acceptable excipient.

12. Method of treatment of at least one selected from the group: aging, frailty or aging related conditions and diseases (ARCD) comprising increasing expression or activation of protein selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3, TUBB1 in patient by therapeutic mean.

13. Method of claim 1 comprising administering an activator of protein selected from the group PABPC4, TRIM58, MSRA, IREB2, UNC45A, VPS33B, PSMD3, TUBB1 or pharmaceutical composition, comprising an activator of such protein.

14. Method of claim 1, comprising administering an agent to increase expression of a gene product encoded from at least one gene selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1.

15. Pharmaceutical composition, comprising an activator of protein selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1.

16. Pharmaceutical composition of claim 13, wherein activator is a small molecule, peptide, aptamer, antibody or protein.

17. Pharmaceutical composition, comprising an agent to increase expression of a gene product encoded from a gene encoding protein selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1.

18. Pharmaceutical composition of claim 16, wherein agent is a gene therapy.

19. Pharmaceutical composition, comprising an activator of protein selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3, TUBB1 for the treatment of aging, frailty or ARCD.

21. Pharmaceutical composition, comprising protein selected from the group PABPC4 , TRIM58, MSRA, IREB2 , UNC45A, VPS33B, PSMD3 , TUBB1 for the treatment of aging, frailty or ARCD.