Chim Inc

EMERGENCY WATERSHED PROTECTION PROGRAM IN RUTHERFORD CO NC. STREAMBANK AND SHORELINE STABILIZATION ACTIVITIES DUE TO HURRICANE HELEN.

CLINICAL EFFICACY OF THE ANTITUMOR AGENT ONC201 IN GBM

KIDDIO: FOOD FIGHT - TRAINING VEGETABLE PARENTING PRACTICES

CLINICAL EFFICACY EVALUATION OF FIRST-IN-CLASS IMIPRIDONE ONC201 IN RECURRENT TYPE II ENDOMETRIAL CANCER

NEXT-GENERATION RNA SYNTHESIS AND LABELING KITS - SUMMARY: CIRCULAR RNAS ARE AN IMPORTANT CLASS OF RNAS THAT HAVE FUNDAMENTAL CELLULAR FUNCTIONS AND HAVE THE POTENTIAL TO BE NOVEL TYPES OF RNA-BASED THERAPEUTICS. CIRCULAR RNAS ARE DIFFICULT TO SYNTHESIZE AND PURIFY DUE TO LOW YIELDS AFTER GEL EXTRACTION. RESOLVING THESE ISSUES COULD BE A MAJOR BENEFIT TO ACADEMIC AND BIOTECHNOLOGY RESEARCH ON CIRCULAR RNA. THE GOAL OF THIS PROPOSAL IS TO MAKE RNA SYNTHESIS AS SIMPLE AS A DNA PLASMID PREP KIT. TO DO THIS, WE WILL DEVELOP TWO NEW HIGH-IMPACT, MARKET-READY KITS. OUR FIRST KIT IS THE “CHIMERNA IN-CELL CIRCULAR RNA PURIFICATION KIT,” WHICH USES OUR “TORNADO” TECHNOLOGY FOR EXPRESSING RNAS AS A CIRCLE. WHEN USED IN E. COLI, THE TORNADO TECHNOLOGY RESULTS IN THE PRODUCTION OF RNA AT HIGH LEVELS NOT PREVIOUSLY SEEN WITH CONVENTIONAL LINEAR RNAS. THE STABILITY OF CIRCULAR RNA ALLOWS IT TO ACCUMULATE TO HIGH LEVELS IN E. COLI, AND ALSO CONFERS HIGH STABILITY IN VITRO AND WHEN TRANSFECTED INTO MAMMALIAN CELLS, THUS MITIGATING THE PERSISTENT DEGRADATION PROBLEM OF CONVENTIONAL LINEAR RNAS. WE ALSO DEVELOPED A NEW RNA-PURIFICATION APTAMER WHICH WE INCORPORATE INTO OUR CIRCLES TO ACHIEVE HIGH PURITY WITH A SIMPLE ONE-STEP ELUTION PROTOCOL. THUS, OUR KIT WILL OVERCOME THE PROBLEMS OF IN VITRO TRANSCRIPTION: LOW YIELD, COMPLEX ENZYMATIC SYNTHESIS REACTION, RNA DEGRADATION, AND THE PROBLEM OF LABORIOUS RNA PURIFICATION. WE WILL ALSO PREPARE THE CHIMERNA RNA LABELING KIT THAT REPURPOSES A TRNA-MODIFYING ENZYME FOR RNA LABELING. THIS COMPANION PRODUCT, COMPRISING THE ENZYME AND SUITABLE SUBSTRATES, WILL MARKEDLY ENHANCE THE ABILITY TO IMPART BIOTIN, FLUORESCENT DYES, CELL-TARGETING MOIETIES, AND OTHER USEFUL TAGS TO RNA. IN ORDER TO DEVELOP THESE NEW COMMERCIAL PRODUCTS, OUR SPECIFIC AIMS ARE: (1) TO OPTIMIZE A KIT FOR HIGH-YIELD CIRCULAR RNA SYNTHESIS AND PURIFICATION WITHOUT IN VITRO TRANSCRIPTION. WE WILL OPTIMIZE THE E. COLI CELL LINE, CULTURING CONDITIONS, DEXTRAN BINDING AND ELUTION CONDITIONS, AND RNA STORAGE CONDITIONS. WE WILL ALSO ESTABLISH PROTOCOLS, MANUALS, REPRODUCIBILITY AND STABILITY CONDITIONS FOR KITTING; (2) TO DEVELOP AN APPROACH FOR SIMPLE AND EFFICIENT RNA LABELING. WE WILL OPTIMIZE REACTION LABELING CONDITIONS AND TARGET RNA SEQUENCES, DEVELOP PROTOCOLS, MANUALS, AND ESTABLISH STABILITY CONDITIONS THAT WILL ALLOW US TO CREATE A USER-READY RNA LABELING KIT; (3) TO DEVELOP A SYSTEM FOR HIGHLY EFFICIENT ELUTION OF TAG-FREE RNA CIRCLES FROM DEXTRAN BEADS. WE WILL PERFORM PILOT EXPERIMENTS TO TEST A COMPLETELY NEW RNA PURIFICATION KIT INVOLVING ON- BEAD RNA CIRCULARIZATION AND ELUTION TRIGGERED BY A SMALL MOLECULE. THIS SYSTEM IS HIGHLY SIMPLIFIED AND FAST, WITH EVEN FEWER CONTAMINANTS AND PRODUCES RNA WITHOUT ANY AFFINITY TAGS. TAKEN TOGETHER, THIS PROJECT WILL RESULT IN THE FIRST KIT FOR SYNTHESIZING CIRCULAR RNA, AN ESPECIALLY CHALLENGING BUT HIGHLY IMPORTANT TYPE OF RNA. THIS TECHNOLOGY IS EXTENDED WITH OUR INNOVATIVE RNA LABELING KIT, ENABLING RESEARCHERS TO LABEL, TAG, OR TRACK RNAS FOR DIVERSE APPLICATIONS. THESE NEW KITS WILL MARKEDLY ACCELERATE CIRCULAR RNA RESEARCH.

THE CHIMNEY ROCK IRRIGATION DISTRICT (DISTRICT), LOCATED IN SCOTTS BLUFF COUNTY, NEBRASKA, WILL MODERNIZE INFRASTRUCTURE ON THE NORTH PLATTE RIVER DIVERSION STRUCTURE AND IMPROVE THE CHIMNEY ROCK CANALS WATER DELIVERY EFFICIENCIES BY UPDATING BOTH THE HEADGATE AND SPILLWAY STRUCTURES. THE PROJECT WILL ALLOW THE DISTRICT TO REDUCE DIVERSIONS, WHICH IS EXPECTED TO RESULT IN ANNUAL WATER SAVINGS OF 3,748 ACRE-FEET. CONSERVED WATER WILL REMAIN IN THE NORTH PLATTE RIVER, HELPING TO AVOID OVER-APPROPRIATION.

PHASE I/II TRIAL OF ONC201 FOR THE TREATMENT OF MULTIPLE MYELOMA IND121,496 (01/05/2015)

TRANSITIONAL LIVING PROGRAM

A NOVEL ANTIBODY THERAPEUTIC FOR MULTIPLE MYELOMA

PUTNAM COUNTY TRANSITIONAL LIVING PROGRAM FOR RUNAWAY AND HOMELESS YOUTH

TRANSITIONAL LIVING PROGRAM

A NOVEL MULTI-EPITOPE-BASED UNIVERSAL VACCINE AGAINST MULTIPLE CORONAVIRUS VARIANTS OF CONCERN - SUMMARY OVER THE LAST 2 YEARS HUMANITY HAS BEEN CONFRONTING COVID-19 PANDEMIC CAUSED BY THE NEW CORONA VIRUS 2 (SARS-COV-2) INFECTION. MAJOR GAPS: MUTATIONS AND DELETIONS OFTEN OCCUR IN THE GENOME OF SARS-COV-2 (PREDOMINANTLY IN THE SPIKE PROTEIN) RESULTING IN MORE TRANSMISSIBLE AND PATHOGENIC “VARIANTS OF CONCERN” (VOCS) THAT CAN ESCAPE IMMUNITY CONFERRED BY FIRST GENERATION COVID-19 VACCINES. BECAUSE MOST MUTATIONS AND DELETIONS THAT PRODUCED THE 20 KNOWN VOCS ARE CONCENTRATED ON THE SPIKE PROTEIN, THERE IS A RISK THAT CURRENT COVID-19 SUB-UNIT VACCINES BASED ON THE SPIKE PROTEIN WILL FAIL TO PROTECT AGAINST FUTURE VOCS DESPITE INDUCING STRONG VIRUS-SPECIFIC NEUTRALIZING ANTIBODIES AGAINST THE ORIGINAL VIRUS STRAIN. AMONG THE 80 MUTATIONS/DELETIONS PRESENT IN OMICRON VARIANT, 32 MUTATIONS/DELETIONS ARE CONCENTRATED IN THE SEQUENCE SPIKE PROTEIN ALONE. THIS EMPHASIZES TWO MAJOR LIMITATIONS OF CURRENTLY AVAILABLE VACCINES: THE NEED FOR SECOND-GENERATION UNIVERSAL CORONAVIRUS VACCINES THAT (1) TARGET ANTIGENS (AGS) OTHER THAN THE HIGHLY VARIABLE SPIKE PROTEIN; AND (2) INCORPORATE BOTH B- AND T-CELL EPITOPES FROM SPIKE AND NON-SPIKE AGS THAT ARE HIGHLY CONSERVED IN ALL 20 VOCS AND THAT WILL INDUCE STRONG HUMORAL AND CELL-MEDIATED IMMUNE RESPONSES. OUR LONG-TERM GOAL IS TO DEVELOP A POTENT SECOND GENERATION UNIVERSAL COV VACCINE TO STOP/REDUCE SARS-COV-2 INFECTIONS AND DISEASE CAUSED BY MULTIPLE VOCS. PRELIMINARY RESULTS: WE: (1) IDENTIFIED HIGHLY IMMUNOGENIC HUMAN B AND T CELL TARGET EPITOPES FROM THE WHOLE SARS-COV-2 GENOME; (2) CHARACTERIZED HUMAN T CELL EPITOPES FROM THE WHOLE SARS-COV-2 GENOME THAT ARE SELECTIVELY TARGETED BY THE “PROTECTIVE” IMMUNE SYSTEM FROM ASYMPTOMATIC COVID-19 PATIENTS; AND (3) PRODUCED A FIRST PROTOTYPE MULTI-EPITOPE UNIVERSAL COV VACCINE CANDIDATE USING THE VALIDATED MRNA DELIVERY SYSTEM PLATFORM, AND (4) CREATED NOVEL “HUMANIZED” SUSCEPTIBLE HLA-DR/HLA-A*0201/HACE2 TRIPLE TRANSGENIC MOUSE MODEL WITH WHICH TO TEST 7 ADDITIONAL MULTI-EPITOPE UNIVERSAL COV VACCINE CANDIDATES THAT BEAR DIFFERENT HIGHLY CONSERVED HUMAN B AND T CELL EPITOPES SPANNING THE ENTIRE COV GENOME. WE HYPOTHESIZE THAT ONE OR MORE OF OUR 7 UNIVERSAL VACCINE CANDIDATES WILL PROTECT “HUMANIZED” MICE FROM INFECTION AND DISEASE CAUSED BY INTRANASAL INOCULATION WITH SARS-COV-2 A, B, G, D AND OMICRON VOCS. OUR SPECIFIC AIMS ARE: AIM 1: TO DESIGN AND CONSTRUCT 7 ADDITIONAL MRNA-BASED UNIVERSAL VACCINE CANDIDATES THAT WILL INCORPORATE HIGHLY CONSERVED B AND T CELL EPITOPES SELECTED FROM 20 VOCS. AIM 2: TO DETERMINE THE SAFETY, IMMUNOGENICITY, AND PROTECTIVE EFFICACY AGAINST SARS-COV-2 A, B, G, D OR OMICRON VOCS OF 7 MULTI-EPITOPE UNIVERSAL COV VACCINE CANDIDATES DELIVERED INTRANASALLY IN THE “HUMANIZED” HLA-DR/HLA-A*0201/HACE2 MOUSE MODEL. THE DURABILITY OF PROTECTION AND ITS CORRELATION WITH BLOCKING/NEUTRALIZING ANTIBODIES AND THE NUMBER AND FUNCTION OF COV-SPECIFIC CD4+ AND CD8+ TRM CELLS THAT RESIDE IN THE LUNGS AND BRAINS WILL BE DETERMINED. IF SUCCESSFUL, THE LEAD UNIVERSAL COV VACCINE THAT PROTECTS AGAINST MOST OF THE 5 VOCS COULD PROCEED QUICKLY INTO AN FDA PHASE 1 CLINICAL TRIAL

BASIC CENTER PROGRAM FOR RUNAWAY AND HOMELESS YOUTH (RHY) IN BREWSTER, PUTNAM COUNTY, NEW YORK

MULTIFAMILY HOUSING SERVICE COORDINATORS

CHIMAYO WATER SUPPLY SYSTEM

BASIC CENTER PROGRAM

THE PURPOSE OF THIS PROJECT IS TO SUPPORT THE STRENGTHENING OF HABITAT CONNECTIVITY BETWEEN THE MOYEN-BAFING AND BADIAR NATIONAL PARKS TO IMPROVE CONDITIONS FOR WEST AFRICAN CHIMPANZEES BY: (1) INCREASING INVOLVEMENT OF LOCAL POPULATIONS IN THE SUSTAINABLE MANAGEMENT OF NATURAL RESOURCES COMMUNICATIONS, STRENGTHENING LOCAL GOVERNANCE STRUCTURES, AND IMPLEMENTING PARTICIPATIVE CORRIDOR BOUNDARY IDENTIFICATION; AND (2) RESTORING HABITAT CONNECTIVITY BETWEEN IDENTIFIED CHIMPANZEE HOTSPOTS IN THE MOYEN-BAFING AND BADIAR NATIONAL PARKS LANDSCAPE THROUGH CAMERA-TRAP MONITORING OF CHIMPANZEES, ESTABLISHING LAND COVER AND LAND USE BASELINE DATA, REHABILITATING KEY FOREST HABITATS THROUGH NATURAL REGENERATION, AND ESTABLISHING FIREBREAKS AND A FIRE MANAGEMENT PLAN TO ACCELERATE THE REESTABLISHMENT OF DEGRADED HABITAT.

SN4C DRUG FREE COMMUNITIES

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU PROGRAM AND OPERATIONS SUPPORT

R3 CFRP GRANT - CCC TRAINING LOCAL YOUNG ADULTS IN THREE FOREST TYPES

KEY FACTORS FOR CORROSION PROTECTION OF METAL SURFACES WITH BIOFILMS

GREEN CHIMNEYS CHILDREN'S SERVICES ARBOR HOUSE BASIC CENTER PROGRAM - THE BASIC CENTER PROGRAM (BCP) (CY) PROVIDES TEMPORARY SHELTER AND COUNSELING SERVICES TO YOUTH WHO HAVE LEFT HOME WITHOUT PERMISSION OF THEIR PARENTS OR GUARDIANS, HAVE BEEN FORCED TO LEAVE HOME, OR ARE OTHERWISE EXPERIENCING HOMELESSNESS AND MIGHT OTHERWISE ENTER THE LAW ENFORCEMENT, CHILD WELFARE, MENTAL HEALTH, OR JUVENILE JUSTICE SYSTEMS. BCPS WORK TO ESTABLISH OR STRENGTHEN COMMUNITY-BASED PROGRAMS THAT MEET THE IMMEDIATE NEEDS OF RUNAWAY AND HOMELESS YOUTH AND THEIR FAMILIES. BCPS PROVIDE YOUTH UNDER 18 YEARS OF AGE WITH EMERGENCY SHELTER, FOOD, CLOTHING, COUNSELING, AND REFERRALS FOR HEALTH CARE. BCPS CAN PROVIDE UP TO 21 DAYS OF SHELTER FOR YOUTH AND SEEK TO REUNITE YOUNG PEOPLE WITH THEIR FAMILIES WHENEVER POSSIBLE, OR TO LOCATE APPROPRIATE ALTERNATIVE PLACEMENTS.

SYNTHETIC BIOLOGY APPROACHES FOR BIO-ORTHOGONAL LABELING OF CIRCULAR RNAS - SUMMARY THE KEY CHALLENGES FOR RNA THERAPEUTICS ARE DELIVERY AND STABILITY INSIDE OF CELLS. CIRCULAR RNAS THAT LACK A 5’ AND 3’ END ARE RESISTANT TO INTRACELLULAR DEGRADATION, WHICH ALLOWS THEM TO PERSIST FOR MUCH LONGER THAN LINEAR RNAS. MEANWHILE LIPID NANOPARTICLE ENCAPSULATION OF RNA HAS IMPROVED STABILITY IN SERUM AND DELIVERY OF RNAS TO CELLS. HOWEVER, ALL RNA-BASED THERAPIES ARE CURRENTLY LIMITED BY INEFFICIENT ESCAPE FROM ENDOSOMES. EVEN WHEN ENCAPSULATED IN LNPS, LESS THAN 1% OF RNAS ARE ABLE TO EFFICIENTLY ESCAPE FROM ENDOSOMES. YET, EVIDENCE EXISTS THAT ENDOSOMAL ESCAPE OF SIRNAS CAN BE IMPROVED BY CONJUGATING RNA WITH HYDROPHOBIC LIPIDS. THESE GROUPS ARE THOUGHT TO DESTABILIZE THE ENDOSOME MEMBRANE, FACILITATING ESCAPE TO THE CYTOPLASM, WHERE THEY CAN EXERT THEIR THERAPEUTIC EFFECT. WHILE IT IS POSSIBLE TO ADD HYDROPHOBIC LIPIDS TO CHEMICALLY SYNTHESIZED SMALL RNAS, THIS IS MORE DIFFICULT FOR MRNAS AND CIRCULAR RNAS THAT ARE TYPICALLY PRODUCED BY IN VITRO TRANSCRIPTION. CHIMERNA SCIENTISTS HAVE DEVELOPED A HIGHLY EFFICIENT METHOD OF PRODUCING CIRCULAR RNAS IN BACTERIA. CHIMERNA HAS ALSO DEVELOPED A PROPRIETARY AFFINITY TAG TO PURIFY CIRCULAR RNAS FROM CRUDE LYSATES. THE RESULTING WORKFLOW IS RAPID, EFFICIENT, AND SCALABLE, WHILE GENERATING >90% PURE CIRCULAR RNA. CHIMERNA SCIENTISTS HAVE ALSO SHOWN THAT THE LIGATION JUNCTION OF THESE CIRCULAR RNA CAN BE MUTATED SO THAT THEY ARE SITE-SPECIFICALLY AMINO FUNCTIONALIZED BY AN ENDOGENOUS TRNA-GUANINE TRANSGLYCOSYLASE. THIS AMINO FUNCTIONAL GROUP CAN BE CONJUGATED LIPIDS THAT ARE WIDELY AVAILABLE OR ARE SIMPLE TO ACTIVATE FOR CONJUGATION USING A ROUTINE COUPLING METHOD. IN THIS WAY, CHIMERNA IS ABLE TO PRODUCE A VARIETY OF SITE-SPECIFICALLY LIPID-CONJUGATED CIRCULAR RNAS THAT MAY ACCELERATE ENDOSOMAL ESCAPE. IN THIS PROJECT, WE AIM TO 1) OPTIMIZE A BACTERIAL STRAIN AND EXPRESSION CONDITIONS FOR HIGH EFFICIENCY AMINO FUNCTIONALIZATION. THIS WILL INVOLVE KNOCKING OUT GENES DOWNSTREAM OF THE TRANSGLYCOSYLASE AND KNOCKING IN ADDITIONAL COPIES OF UPSTREAM GENES. 2) IMPROVE THE ENDOSOMAL ESCAPE OF RNAS BY SITE-SPECIFIC LIPID CONJUGATION. WE WILL TEST A VARIETY OF LIPID CONJUGATES TO A SMALLER CIRCULAR RNA THAT IS A MIRNA SPONGE, AND A LARGER CIRCULAR MRNA THAT IS TRANSLATED BY CAP-INDEPENDENT TRANSLATION. BOTH RNAS WILL BE ENCAPSULATED USING STANDARD METHODS AND WE WILL TEST EFFICIENCY OF ENDOSOMAL ESCAPE. TAKEN TOGETHER, WE WILL GENERATE A SCALABLE AND LOW-COST METHOD FOR SEMI-SYNTHESIS OF SITE-SPECIFICALLY LABELED CIRCULAR RNAS. WE WILL LEVERAGE THIS APPROACH TO SOLVE THE ENDOSOMAL ESCAPE CHALLENGES OF RNA THERAPEUTICS DELIVERY.

COMMUNITY OUTREACH CENTER STREET OUTREACH PROGRAM

STREET OUTREACH PROGRAM

BASIC CENTER PROGRAM GRANT - ARBOR HOUSE

BASIC CENTER PROGRAM

HIGHLY SENSITIVE CHIMERISM TESTING TO DETECT EARLY LEUKEMIA RELAPSE POST-ALLO-TRANSPLANTATION

DEVELOPMENT OF CIRCRNA MANUFACTURING PLATFORM IN YEAST - SUMMARY: CIRCULAR RNAS (CIRCRNAS) ARE A NOVEL CLASS OF RNAS THAT HOLD IMMENSE POTENTIAL AS THERAPEUTICS DUE TO THEIR UNIQUE CELLULAR FUNCTIONS. HOWEVER, THE CHALLENGES ASSOCIATED WITH THEIR SYNTHESIS AND PURIFICATION HAVE IMPEDED THEIR RESEARCH AND DEVELOPMENT. CHIMERNA PROPOSES TO DEVELOP A PLATFORM TECHNOLOGY USING YEAST TO MANUFACTURE HIGH-QUALITY CIRCRNAS FOR USE IN RESEARCH, THERAPEUTICS, AND DIAGNOSTICS. THE PROPOSED TECHNOLOGY BUILDS UPON CHIMERNA'S TORNADO TECHNOLOGY FOR EXPRESSING RNAS AS A CIRCLE IN CELLS. WHEN USED IN E. COLI, THE TORNADO TECHNOLOGY RESULTS IN THE PRODUCTION OF RNA AT HIGH LEVELS NOT PREVIOUSLY SEEN WITH CONVENTIONAL LINEAR RNAS. THE STABILITY OF CIRCULAR RNA ALLOWS IT TO ACCUMULATE TO HIGH LEVELS IN E. COLI, AND ALSO CONFERS HIGH STABILITY IN VITRO AND WHEN TRANSFECTED INTO MAMMALIAN CELLS, THUS MITIGATING THE PERSISTENT DEGRADATION PROBLEM OF CONVENTIONAL LINEAR RNAS. THE PROJECT ALSO UTILIZES A PROPRIETARY AFFINITY TAG THAT IS ENCODED INTO THE CIRCRNA MAKING DOWNSTREAM PURIFICATION EASIER. THIS TECHNOLOGY RESOLVES KEY PROBLEMS ASSOCIATED WITH CURRENT CIRCULAR RNA SYNTHESIS METHODS THAT USE IN VITRO TRANSCRIPTION FOR PRODUCTION. HOWEVER, PRODUCTION OF CIRCRNA IN E. COLI RESULTS IN HIGH LEVELS OF LPS, WHICH IS DIFFICULT TO REMOVE AND NOT ACCEPTABLE FOR THERAPEUTIC INDICATIONS. THE CURRENT PROPOSAL AIMS TO ENGINEER A YEAST STRAIN CAPABLE OF PRODUCING CIRCRNAS AT HIGH YIELDS. UNLIKE BACTERIA, YEAST DO NOT CONTAIN LPS, WHICH IS DIFFICULT TO REMOVE IN DOWNSTREAM PURIFICATION APPLICATIONS. MOREOVER, YEAST HAS BEEN EXTENSIVELY USED FOR MANUFACTURING MANY BIOACTIVE COMPOUNDS SUCH AS PROTEINS AND LIPIDS. THIS MAKES YEAST AN IDEAL ORGANISM IN WHICH TO DEVELOP A CIRCRNA MANUFACTURING PLATFORM. THE SPECIFIC AIMS OF THE PROJECT ARE: (1) - TO ENGINEER A YEAST STRAIN THAT CAN BE INDUCED TO EXPRESS CIRCULAR RNA AT HIGH YIELDS: THIS AIM INVOLVES ENGINEERING MULTIPLE YEAST STRAINS TO PRODUCE CIRCRNAS AND TESTING THEIR YIELD UNDER VARIOUS INDUCIBLE PROMOTERS. THE YEAST STRAIN WILL BE FURTHER OPTIMIZED BY INTRODUCING RNA PROCESSING ENZYMES REQUIRED FOR MAXIMUM CIRCULARIZATION EFFICIENCY; (2) TO BENCHMARK CIRCRNA MANUFACTURING TO EXISTING MANUFACTURING TECHNOLOGIES: THE SECOND AIM OF THE PROJECT INVOLVES COMPARING THE YIELD AND COST PER GRAM OF RNA PRODUCED IN YEAST VERSUS TRADITIONAL IVT. THE RESEARCHERS WILL ALSO EXAMINE PROTEIN EXPRESSION AND RNA HALF-LIFE FROM A CIRCULAR MRNA VERSUS A LINEAR MRNA FOR TOTAL PROTEIN OUTPUT IN MAMMALIAN CELLS. FINALLY, THEY WILL MEASURE INFLAMMATORY RESPONSES TO TRANSFECTED CIRCRNAS VERSUS LINEAR MRNAS. TAKEN TOGETHER, THE DEVELOPMENT OF A YEAST MANUFACTURING PLATFORM FOR SYNTHESIZING CIRCRNAS HOLDS IMMENSE PROMISE FOR THE PRODUCTION OF THIS HIGHLY IMPORTANT TYPE OF RNA. THE PROPOSED TECHNOLOGY WILL GREATLY REDUCE THE COST OF PRODUCING CIRCRNAS WHILE ALSO SIMPLIFYING THE PURIFICATION AND DOWNSTREAM PROCESSING. THIS NEW MANUFACTURING PLATFORM WILL ACCELERATE THE ENTRY OF CIRCRNAS FOR MEDICAL USE, THEREBY ADVANCING THE FIELD OF RNA THERAPEUTICS.

BASIC CENTER PROGRAM

CHIMAYO CONSERATION CORPS DEVELOPING LOCAL CAPACITY TO RESTORE FOREST HEALTH

DRUG-FREE COMMUNITIES (DFC) SUPPORT PROGRAM ? NON-COMPETING CONTINUATION - DRUG-FREE COMMUNITIES (DFC) SUPPORT PROGRAM - NON-COMPETING CONTINUATION

A NOVEL TDP-43-TARGETING CIRCULAR RNA TO TREAT AMYOTROPHIC LATERAL SCLEROSIS (ALS) - SUMMARY AMYOTROPHIC LATERAL SCLEROSIS (ALS) IS A FATAL NEURODEGENERATIVE DISEASE CHARACTERIZED BY INCLUSION BODIES CONTAINING THE TDP-43 PROTEIN IN THE CYTOPLASM OF MOTOR NEURONS. THESE INCLUSION BODIES ARE CAUSED BY TDP- 43 AGGREGATION, WHICH IS CAUSED BY PATHWAYS OR MUTATIONS THAT CAUSE TDP-43 TO LOCALIZE TO THE CYTOPLASM. TDP-43 IS AN RNA-BINDING PROTEIN AND ITS ABILITY TO BIND MRNA IS A CRITICAL STEP IN THE PROCESS THAT ULTIMATELY LEADS TO TDP-43 AGGREGATES. WHEN TDP-43 BINDS CELLULAR RNAS, IT CAN “PHASE SEPARATE” AND BECOME ENRICHED IN STRESS GRANULES, WHERE TDP-43 SLOWLY FORMS INSOLUBLE AGGREGATES. A WIDELY ACCEPTED THERAPEUTIC GOAL IS TO PREVENT TDP-43 FROM UNDERGOING PHASE SEPARATION INTO STRESS GRANULES, SINCE THIS IS A PREREQUISITE FOR TDP-43 AGGREGATION. TO BLOCK TDP-43 PHASE SEPARATION, WE ARE USING RNA APTAMERS THAT BIND TDP-43’S RNA-BINDING DOMAIN AND THUS ACT AS A “DECOY” TO BLOCK TDP-43 FROM BINDING TO CELLULAR MRNA. HOWEVER, RNA APTAMERS ARE RAPIDLY DEGRADED IN THE CYTOSOL. CHIMERNA SCIENTISTS HAVE DEVELOPED AN INNOVATIVE EXPRESSION SYSTEM THAT ALLOWS RNA APTAMERS TO RAPIDLY BE CONVERTED INTO “CIRCULAR” RNAS IN CELLS, THUS MAKING THEM RESISTANT TO CELLULAR EXONUCLEASES. THIS DRAMATICALLY INCREASES RNA APTAMER STABILITY, LEADING TO EXPRESSION LEVELS THAT ARE AT LEAST 100 TIMES HIGHER THAN ANY PREVIOUS EXPRESSION SYSTEM. USING THIS SYSTEM, WE FOUND THAT CIRCULAR TDP-43-BINDING APTAMERS CAN BLOCK PHASE SEPARATION OF TDP-43 USING AN OPTOGENETIC TDP-43 PHASE-SEPARATION ASSAY. SINCE THE CIRCULAR RNAS ARE CYTOSOLIC, THEY SELECTIVELY BLOCK THE CYTOSOLIC FORM OF TDP-43 WITHOUT AFFECTING THE NORMAL FUNCTION OF TDP-43 IN THE NUCLEUS. THE CRITICAL QUESTION IS WHETHER TDP-43-BINDING APTAMERS WILL PREVENT TDP-43 AGGREGATION, TOXICITY, AND NEURODEGENERATION IN DISEASE- RELEVANT MODELS. TO TEST THIS, THE SPECIFIC AIMS OF THIS PROPOSAL ARE: (1) TO EVOLVE TDP-43 APTAMERS FOR HIGHER AFFINITY AND LOWEST IC50 FOR BLOCKING PHASE SEPARATION. WE WILL USE DIRECTED EVOLUTION TO EVOLVE HIGH-AFFINITY TDP-43 APTAMERS. WE WILL USE OUR OPTOGENETIC PLATFORM FOR INDUCING TDP-43 PHASE SEPARATION IN CELLS TO CALCULATE IC50 VALUES FOR THE TOP EVOLVED APTAMERS. THESE EXPERIMENTS WILL REVEAL THE APTAMERS THAT HAVE THE GREATEST POTENTIAL TO DISRUPT TDP-43 PHASE SEPARATION. (2) TO TEST THE ABILITY OF CIRCULAR TDP-43 APTAMERS TO BLOCK PHASE SEPARATION, AGGREGATION, AND TOXICITY OF TDP-43 IN HUMAN IPS NEURONS. HERE, WE WILL USE IPS-DERIVED ALS MOTOR NEURONS THAT EXHIBIT TDP-43 AGGREGATES, MARKERS OF AGGREGATE TOXICITY, AND INCREASED SUSCEPTIBILITY TO OXIDATIVE STRESS-MEDIATED CELL DEATH. WE WILL DETERMINE IF TDP-43 APTAMERS CAN BLOCK THESE KEY PARAMETERS OF TDP-43 AGGREGATE TOXICITY, THUS PROVIDING CRITICAL DATA ABOUT THE VALIDITY OF OUR APTAMER APPROACH USING DISEASE-RELEVANT MODEL. OVERALL, THESE EXPERIMENTS WILL TEST A NEW CONCEPT FOR BLOCKING TDP-43 AGGREGATION USING HIGHLY STABLE CIRCULAR TDP-43 APTAMERS, THAT WILL BE TESTED USING AN OPTOGENETIC PHASE SEPARATION ASSAY AND ALS IPS-DERIVED MOTOR NEURONS.

CIRCULAR RNA APTAMERS TO REGULATE IRON HOMEOSTASIS IN IRON OVERLOAD DISORDERS - SUMMARY: IRON OVERLOAD DISORDERS ARE CAUSED BY HOMEOSTATIC IMBALANCE OF IRON IN THE LIVER. EXCESS IRON PRODUCES REACTIVE OXYGEN SPECIES THAT INDUCE INFLAMMATION, FIBROSIS, AND CAUSE FERROPTOSIS, AN IRON-DEPENDENT FORM OF CELL DEATH. REDUCING IRON LEVELS HAS A THERAPEUTIC BENEFIT. ALTHOUGH CHELATING IRON IS APPEALING FOR THESE DISORDERS, IRON CHELATORS EXHIBIT POOR PHARMACOKINETICS AND INDUCE A COMPENSATORY IRON UPTAKE RESPONSE IN CELLS. IN THIS PROPOSAL, WE ARE PROPOSING A COMPLETELY NOVEL APPROACH FOR REMOVING IRON FROM HEPATOCYTES. OUR APPROACH TARGETS IRP1/2, THE PROTEINS THE CONTROL IRON HOMEOSTASIS. IRP1/2 BINDS “IRE” SEQUENCES FOUND IN CERTAIN MRNAS ONLY WHEN IRON LEVELS ARE LOW. IRP1/2 BINDING TO MRNA LEADS TO TRANSLATION OF PROTEINS THAT CAUSE IRON INFLUX IN CELLS. SINCE IRP1/2 IS ABNORMALLY ACTIVATED IN IRON OVERLOAD DISORDERS, BLOCKING THE IRP1/2'S RNA-BINDING ACTIVITY COULD REDUCE INTRACELLULAR IRON AND REDUCE FERROPTOSIS. SINCE IRP1/2 CANNOT BE TARGETED WITH SMALL MOLECULES OR SIRNA DUE TO AN ESSENTIAL FUNCTION OF IRP1, WE ARE PROPOSING A NEW THERAPEUTIC CONCEPT: WE ARE USING IRE SEQUENCES AS “DECOYS” TO BLOCK IRP1/2 FROM BINDING MRNA, THUS SIMULATING A “HIGH IRON” STATE, AND CAUSING THE CELL TO REDUCE CELLULAR IRON LEVELS. THIS APPROACH WOULD NORMALLY BE IMPOSSIBLE SINCE SMALL RNAS, LIKE THE IRE, ARE HIGHLY UNSTABLE IN CELLS. HOWEVER, CHIMERNA SCIENTISTS HAVE DEVELOPED A NEW STRATEGY TO STABILIZE THE IRE BY SYNTHESIZED THIS RNA AS AN RNA CIRCLE. WE FIND THAT THESE CIRCULAR IRES INDUCE A ROBUST IRON REMOVAL PROGRAM AND CAUSE CELLS TO BECOME RESISTANT TO FERROPTOSIS. AT THIS POINT, THE MAJOR QUESTION IS CAN THESE CIRCULAR IRES BE EFFECTIVELY TARGETED TO HEPATOCYTES AND DO THEY REACH A THERAPEUTIC CONCENTRATION. IN ORDER TO TEST THIS IDEA, THE SPECIFIC AIMS OF THIS PROPOSAL ARE: (1) TO OPTIMIZE THE DELIVERY AND DOSE OF CIRCULAR IRE RNA FOR PERTURBING CELLULAR IRON HOMEOSTASIS. WE WILL SYNTHESIZE CIRCULAR IRES WITH A TRIANTENNARY N- ACETYLGALACTOSAMINE THAT ALLOWS THE CIRCRNAS TO BE PREFERENTIALLY TAKEN UP BY THE LIVER (2) TO TEST THE ABILITY OF CIRCULAR IRES TO REDUCE FERROPTOSIS IN CULTURE MODELS OF IRON OVERLOAD DISORDERS. HERE, WE WILL USE AN IRON OVERLOAD DISORDER MODEL OF PRIMARY HUMAN HEPATOCYTES TREATED WITH FERRIC AMMONIUM CITRATE (FAC). PRIMARY HEPATOCYTES WILL BE TRANSFECTED WITH TRI(GALNAC)-MODIFIED CIRCULAR IRES. THESE COMPARISONS WILL ALLOW US TO DETERMINE WHETHER CIRCULAR IRES ARE AS, OR POTENTIALLY MORE EFFECTIVE, THAN STANDARD CHELATOR-BASED APPROACHES. OVERALL, THIS APPLICATION WILL (1) CREATE A FUNDAMENTALLY NEW TYPE OF RNA THERAPEUTIC; (2) TARGET CELLULAR IRON HOMEOSTASIS FOR THE FIRST TIME; AND (3) PROVIDE A FUNDAMENTALLY NEW APPROACH TO TREAT IRON OVERLOAD DISORDERS.

SN4C HOLCOMB COMMUNITY - PROJECT ABSTRACT SUMMARY: SN4C HOLCOMB COMMUNITY. THROUGH THIS PROJECT, WE WILL STRENGTHEN COMMUNITY COLLABORATION AND BUILD CAPACITY AROUND SUBSTANCE USE PREVENTION IN SOUTHERN NEW CASTLE COUNTY. IMPLEMENT PREVENTION EDUCATION AND AWARENESS FOR YOUTH AGES 9-20, THEIR FAMILIES, AND OLDER ADULTS. ENHANCE THE ABILITY OF THE COMMUNITY TO IDENTIFY AND ADDRESS GAPS IN SERVICE THROUGH DATA COLLECTION, OUTREACH AND CAPACITY. DECREASE YOUTH ACCESS TO SUBSTANCES THROUGH COMPLIANCE PARTNERSHIPS WHILE FOCUSING ON EMPOWERING YOUTH THROUGH PROVIDING PREVENTION BASED LEADERSHIP OPPORTUNITIES. SOUTHERN NEW CASTLE COUNTY COMMUNITIES COALITION (SN4C) IS A COMMUNITY GROUP COMPOSED OF INDIVIDUALS AND ORGANIZATIONS WHO BELIEVE IN OUR MISSION TO PREVENT YOUTH SUBSTANCE USE AND ABUSE IN ORDER TO PRODUCE HEALTHY STABLE, FAMILY ORIENTED COMMUNITIES. THE PRIORITY POPULATION WILL BE DEFINED AS CHILDREN AND YOUTH AGES 9 TO 20, THEIR FAMILIES, OLDER ADULTS, AND COMMUNITIES. THE GEOGRAPHIC AREA FOR THE PROPOSED PREVENTION STRATEGIES WILL BE SOUTHERN NEW CASTLE COUNTY, WHICH IS INCLUSIVE OF MIDDLETOWN (19709) OUR LARGEST COMMUNITY, ODESSA, (19730), TOWNSEND (19734), SOUTHWESTERN PORTIONS OF BEAR (19701) AND PORTIONS OF NEWARK (19701, 19702). SN4C STARTED AS 4 MEMBERS AT A KITCHEN TABLE WANTING TO DO MORE TO HELP OUR COMMUNITIES’ YOUTH AVOID THE NEGATIVE CONSEQUENCES OF DRUGS AND ALCOHOL. TODAY WE HAVE QUADRUPLED IN SIZE AND IN USING LOCAL DATA AS A GUIDE WE AGREED TO ADDRESS ALCOHOL, TOBACCO AND MARIJUANA USE. THE GOALS AND OBJECTIVES FOR THIS PROJECT ARE TO STRENGTHEN COMMUNITY COLLABORATION AND SUPPORT LOCAL EFFORTS TO PREVENT YOUTH SUBSTANCE USE THROUGH DECREASING ACCESS AND INCREASING EDUCATION AND AWARENESS FOR FAMILIES, OLDER ADULTS/VETERANS, AND COMMUNITIES. THE COALITION WILL ACHIEVE THESE GOALS THROUGH THE STRATEGIC PREVENTION FRAMEWORK AND THOROUGH EXPERIENCES WITH SEVEN STRATEGIES FOR COMMUNITY CHANGE. WE’LL INCREASE CAPACITY TO PROMOTE AWARENESS OF PREVENTION EFFORTS. ENHANCE THE ABILITY OF THE COMMUNITY TO IDENTIFY GAPS IN NEEDS THROUGH DATA COLLECTION, OUTREACH AND CAPACITY BUILDING. FORM A WORKGROUP TO CREATE THE INAUGURAL MARIJUANA PRESENTATION WITH SUPPORT FROM THE DIVISION OF ALCOHOL AND TOBACCO ENFORCEMENT (DATE). AS MEASURED BY THE NUMBER OF WORKGROUP MEETINGS. BY 2028, CREATE AN INAUGURAL MARIJUANA PRESENTATION FOR THE PREVENTION FIELD IN PARTNERSHIP AND DATE. AS MEASURED BY 1 PRESENTATION. BY 2031, INCREASE OUTREACH EFFORTS TO OLDER ADULTS/VETERAN POPULATIONS. INCREASE INFORMATION DISSEMINATION AND AWARENESS AROUND MARIJUANA AND RECENT STATE APPROVAL OF RECREATIONAL MARIJUANA TO ADULT POPULATIONS. IN 2028, ESTABLISH MEDIA CAMPAIGNS FOR EACH TARGET POPULATION OF VETERANS, OLDER ADULTS AND 21+ POPULATIONS AROUND SAFE STORAGE AND DISPOSAL OF MARIJUANA, ALONG WITH RISK AWARENESS FOR USE WITH PRESCRIPTION DRUGS AS MEASURED BY CAMPAIGN MATERIAL CREATED. INCREASE NUMBER OF SCHOOL-BASED PREVENTION YOUTH-LED COALITION GROUPS BY 2031. PREVENT YOUTH SUBSTANCE USE OF ALCOHOL, MARIJUANA, AND E-CIGARETTES/ VAPE PRODUCTS. BY 2031, INCREASE YOUTH PERCEPTION OF GREAT RISK FOR MARIJUANA USE BY 4% AS MEASURED BY THE DELAWARE SCHOOL SURVEY. BY 2031, INCREASE YOUTH PARTICIPATION IN TRAININGS AND LEADERSHIP DEVELOPMENT BY 10%. AS MEASURED BY YOUTH ATTENDANCE LOGS. IN 2031 INCREASE PERCEPTION OF GREAT RISK OF VAPING BY 5% FOR YOUTH MEASURED BY THE DELAWARE SCHOOLS SURVEY (DSS 2022). WE ARE COMMITTED TO BUILDING PREVENTION CAPACITY AND DECREASING YOUTH ACCESS, INCREASING EDUCATION AND AWARENESS AROUND ALCOHOL, TOBACCO/VAPE PRODUCTS AND MARIJUANA. THE PROPOSED NUMBER OF PEOPLE TO BE SERVED AS A RESULT OF THE AWARD OF THIS GRANT: ESTIMATING IMPACTS OF 3,200 ANNUALLY AND FOR THE ENTIRE DURATION OR LIFETIME OF THE PROJECT 16,000 WITH MEDIA IMPRESSION RATES OVER 70,000.

LAMP BEGINNING AND SOCIALLY DISADVANTAGED FARMERS OR RANCHERS--MANDATORY

TRANSBOUNDARY BIODIVERSITY CONSERVATION OF THE TAI-SAPO FOREST COMPLEX IN COLED'LVOIRE AND LIBERIA

SEC. 9007 REAP-RENEW ENERGY SYS GRANTS (MAN)

CHIMERIC FVIIA

NON-THROMBOGENIC PROPERTIES OF CHIMERIC FVIIA

CIRCULAR RNA AS A PLATFORM FOR GENOME-WIDE MICRORNA SPONGE LIBRARIES

USING HIGHLY EXPRESSED CIRCULAR RNAS TO SUBSTANTIALLY ENHANCE PROTEIN EXPRESSION YIELDS IN MAMMALIAN CELLS

THE LOCAL COMMUNITY CAPACITY DEVELOPMENT ACTIVITY WILL PROVIDE TECHNICAL ASSISTANCE TO ENABLE LOCAL COMMUNITIES SURROUNDING THE MARSHALL WETLANDS TO INCREASE HOUSEHOLD INCOMES THROUGH SUSTAINABLE, AGRICULTURE-BASED LIVELIHOODS THAT SUPPORT THE LCRP SANCTUARY AND CONSERVATION CENTER (THE SANCTUARY) LOCATED IN MARSHALL, MARGIBI COUNTY.

FY2018 GREAT APE CONSERVATION FUND

THE PURPOSE OF THIS PROJECT IS TO PROTECT THE SECOND LARGEST POPULATION OF ENDANGERED WESTERN CHIMPANZEES IN LIBERIA THROUGH GAZETTEMENT OF THE KRAHN-BASSA PROPOSED PROTECTED AREA (KBPPA) AS LIBERIA'S LARGEST NATIONAL PARK BY: (1) INCREASING THE NUMBER OF COMMUNITY ECOMONITORING TEAMS, IMPLEMENTING SMART DATA COLLECTION, AND SHARING OF INFORMATION WITH THE PARK AUTHORITIES; (2) INCREASING LOCAL COMMUNITIES' AWARENESS OF HUMAN-CHIMP CONFLICT AND HOW TO AVOID IT; AND (3) IMPROVING COMMUNITY ECOMONITORING COLLABORATION WITH LIBERIA'S WILDLIFE CRIME TASK FORCE THROUGH INCREASED TRAINING, COMMUNICATION, AND JOINT MONITORING ACTIVITIES.

FY2018 GREAT APE CONSERVATION FUND

LAMP VALUE ADDED PRODUCER GRANT--MANDATORY

STREET OUTREACH PROGRAM

GREAT APE CONSERVATION FUND 2017

PROTECTING CONSERVATION PRIORITY AREA

TAS::57 3600::TAS "ULTRACOLD POLAR MOLECULES -- NEW PHASES OF MATTER FOR QUANTUM INFORMATION AND QUANTUM CONTROL"

ECONOMIC DEVELOPMENT INITIATIVE-SPECIAL PROJECT NEIGHBORHOOD INITIATIVE AND MISCELLANEOUS GRANTS

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU OPERATION SUPPORT

IMPROVING WEST AFRICAN CHIMPANZEE CONSERVATION THROUGH PROTECTED AREA MANAGEMENT IN THE GREBO NATIONAL PARK

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

IMPROVING WEST AFRICAN CHIMPANZEE CONSERVATION THROUGH PROTECTED AREA MANAGEMENT IN THE GREBO NATIONAL PARK

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU PROGRAM AND OPERATIONS SUPPORT

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU OPERATION SUPPORT

TAS::57 3600::TAS "MODELLING FERROELECTRIC NANOPARTICLES IN NEMATIC LIQUID CRYSTALS (FERNANO)."

CONTINUUM OF CARE PROGRAM

FARM TO SCHOOL GRANT PROGRAM

THE PURPOSE OF THIS GRANT IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU PROJECT SUPPORT

AMENDMENT TO PROVIDE ADDITIONAL TRAVEL FUNDS

THE PURPOSE OF THIS GRANT IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU PROJECT SUPPORT

LANDSCAPE CONSERVATION FOR CHIMPANZEES IN THE BAFING RIVER AREA

MAKE NO LITTLE PLANS: DANIEL BURNHAM AND THE AMERICAN CITY

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE BALTI PROGRAM SUPPORT

ARRA #CIM 0231-08F REGIONWIDE HISTORIC BUILDINGS RESTORATIONS

PURPOSE: THE CONTINUUM OF CARE (COC) PROGRAM IS DESIGNED TO PROMOTE COMMUNITY-WIDE COMMITMENT TO THE GOAL OF ENDING HOMELESSNESS; PROVIDE FUNDING FOR EFFORTS BY NONPROFIT PROVIDERS, STATES, AND LOCAL GOVERNMENTS TO QUICKLY HOUSE HOMELESS INDIVIDUALS AND FAMILIES WHILE MINIMIZING THE TRAUMA AND DISLOCATION CAUSED TO HOMELESS INDIVIDUALS, FAMILIES, AND COMMUNITIES BY HOMELESSNESS; PROMOTE ACCESS TO AND EFFECTIVE UTILIZATION OF MAINSTREAM PROGRAMS BY HOMELESS INDIVIDUALS AND FAMILIES; AND OPTIMIZE SELF-SUFFICIENCY AMONG INDIVIDUALS AND FAMILIES EXPERIENCING HOMELESSNESS. THE MOST RECENT COC AWARD ANNOUNCEMENT LISTING AWARDS BY STATE AND COC IS ACCESSIBLE AT HTTPS://WWW.HUD.GOV/PROGRAM_OFFICES/COMM_PLANNING/COC/AWARDS. SELECT THE LINK UNDER THE FUNDING AND AWARD INFORMATION SECTION FOR THE APPROPRIATE FISCAL YEAR.; ACTIVITIES TO BE PERFORMED: CONTINUUM OF CARE PROGRAM FUNDS MAY BE USED TO PAY FOR THE ELIGIBLE COSTS USED TO ESTABLISH AND OPERATE PROJECTS UNDER FIVE PROGRAM COMPONENTS: (1) PERMANENT HOUSING, WHICH INCLUDES PERMANENT SUPPORTIVE HOUSING FOR PERSONS WITH DISABILITIES, AND RAPID REHOUSING; (2) TRANSITIONAL HOUSING; (3) SUPPORTIVE SERVICES ONLY; (4) HOMELESS MANAGEMENT INFORMATION SYSTEMS (HMIS), AND (5) IN SOME CASES, HOMELESSNESS PREVENTION. THIRTEEN TYPES OF ASSISTANCE MAY BE PROVIDED THROUGH THE CONTINUUM OF CARE (COC) PROGRAM: (1) COC PLANNING ACTIVITIES/COSTS FOR DESIGNING AND CARRYING OUT A COLLABORATIVE PROCESS FOR THE DEVELOPMENT OF AN APPLICATION TO HUD; (2) UNITED FUNDING AGENCY (UFA) COSTS FOR FISCAL CONTROL AND ACCOUNTING NECESSARY TO ASSURE THE PROPER DISBURSAL OF, AND ACCOUNTING FOR, FEDERAL FUNDS AWARDED TO SUBRECIPIENTS UNDER THE CONTINUUM OF CARE PROGRAM, (3) ACQUISITION OF REAL PROPERTY (INCLUDING STRUCTURES) FOR USE IN THE PROVISION OF HOUSING OR SUPPORTIVE SERVICES; (4) REHABILITATION OF STRUCTURES TO PROVIDE HOUSING OR SUPPORTIVE SERVICES; (5) NEW CONSTRUCTION, INCLUDING THE BUILDING OF A NEW STRUCTURE OR BUILDING AN ADDITION TO AN EXISTING STRUCTURE FOR USE AS SUPPORTIVE HOUSING; (6) LEASING OF A STRUCTURE OR STRUCTURES, OR PORTIONS THEREOF, TO PROVIDE HOUSING OR SUPPORTIVE SERVICES; (7) RENTAL ASSISTANCE, WHICH MAY BE SHORT-TERM, MEDIUM-TERM, OR LONG-TERM, AS WELL AS TENANT-BASED, PROJECT-BASED, OR SPONSOR-BASED, FOR TRANSITIONAL OR PERMANENT HOUSING; (8) SUPPORTIVE SERVICES TO ASSIST PROGRAM PARTICIPANTS OBTAIN AND MAINTAIN HOUSING; (9) OPERATING COSTS OF SUPPORTIVE HOUSING; (10) COSTS OF IMPLEMENTING AND OPERATING HMIS; (11) PROJECT ADMINISTRATIVE COSTS; (12) RELOCATION COSTS; AND (13) INDIRECT COSTS IN ACCORDANCE WITH 2 CFR PARTS 200, AS APPLICABLE. IN ADDITION TO USING GRANT FUNDS FOR THE ELIGIBLE COSTS DESCRIBED ABOVE, RECIPIENTS AND SUBRECIPIENTS IN CONTINUUMS OF CARE DESIGNATED AS HIGH PERFORMING COMMUNITIES MAY ALSO USE GRANT FUNDS TO PROVIDE HOUSING RELOCATION AND STABILIZATION SERVICES AND SHORT- AND/OR MEDIUM-TERM RENTAL ASSISTANCE TO INDIVIDUALS AND FAMILIES AT RISK OF HOMELESSNESS AS SET FORTH IN 24 CFR 576.103 AND 24 CFR 576.104, IF NECESSARY TO PREVENT THE INDIVIDUAL OR FAMILY FROM BECOMING HOMELESS. LIMITATION ON USE OF FUNDS: NO ASSISTANCE PROVIDED UNDER PROGRAM (OR ANY STATE OR LOCAL GOVERNMENT FUNDS USED TO SUPPLEMENT THIS ASSISTANCE) MAY BE USED TO REPLACE STATE OR LOCAL FUNDS PREVIOUSLY USED, OR DESIGNATED FOR USE, TO ASSIST HOMELESS PERSONS OR PERSONS AT-RISK OF HOMELESSNESS.; EXPECTED OUTCOMES: DECREASE IN THE NUMBER INDIVIDUALS AND FAMILIES EXPERIENCING HOMELESSNESS, MORE SPECIFICALLY USING PERFORMANCE INDICATORS SUCH AS THE LENGTH OF TIME HOMELESS, RETURNS TO HOMELESSNESS OVER TIME, AND EXITS TO PERMANENT HOUSING. COC PERFORMANCE PROFILE REPORTS CAN BE FOUND AT HTTPS://WWW.HUDEXCHANGE.INFO/PROGRAMS/COC/COC-PERFORMANCE-PROFILE-REPORTS/.; INTENDED BENEFICIARIES: INDIVIDUALS AND FAMILIES EXPERIENCING HOMELESSNESS.; SUBRECIPIENT ACTIVITIES: THE SUBRECIPIENT ACTIVITIES ARE UNKNOWN AT THE TIME OF AWARD.

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE BALTI OPERATION SUPPORT

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE BALTI OPERATION SUPPORT

ASSISTANCE TO FIREFIGHTERS GRANT

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT MOLDOVAN AND UKRAINIAN YOUTH FOR IDEA INCLUSION DIVERSITY EQUITY AND ACCESSIBILITY PROGRAM

CONTINUUM OF CARE PROGRAM

CONTINUUM OF CARE PROGRAM

THE PURPOSE OF THIS GRANT IS TO SUPPORT THE PROJECT AMERICA HOUSE BALTI PROJECT SUPPORT

SN4C DRUG FREE COMMUNITIES

GREAT APE CONSERVATION FUND 2017

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU PROJECT SUPPORT

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE CHISINAU PROGRAMMING SUPPORT

SEC. 9007 REAP-ENERGY EFFICIENCY IMPROVEMENTS GRANTS (MAN)

CONTINUUM OF CARE PROGRAM

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE BALTI PROGRAMMING SUPPORT

TO PROMOTE HIV/AIDS PREVENTION PROGRAMS FOR POLICE, COMMERCIAL SEX WORKERS, THEIR CLIENTS AND TRUCK DRIVERS IN CHIMOIO

PROJECT WILL LEVERAGE EXISTING COMMUNITY NETWORKS, AGENCY AND PARTNERSHIP CONNECTIONS, AND PAST EXPERIENCES TO ESTABLISH A LOCAL WASTE AND POLLUTION

PROVIDE FUNDS TO SUPPORT A ONE MONTH LONG EXHIBIT THAT CELEBRATES US CULTURE WITH ITS INTERACTIVE TAKE ON SPORTS AND ENTREPRENEURSHIP.

TO SUPPORT THE 2018 U.S. CULTURE MONTH EXHIBIT AND COVER THE ENTRY FEE AND SNACK FOR 4,000 UNDERPRIVILEGED CHILDREN.

THE PURPOSE OF THIS AWARD IS TO SUPPORT THE PROJECT AMERICA HOUSE BALTI PROJECT SUPPORT