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Awwa Chaga Qambara Taqwa
Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
Medicine & Pharmacology

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Potensi CRISPR-Cas9 Terkonjugasi Sistem Pengantar Vesikel Ekstraseluler sebagai Strategi Terapeutik Penyakit HIV dengan Metode Genome Editing untuk Pengobatan Masa Depan Penyakit HIV Muhammad Rizky Hidayatullah; Salwa Adilah Ningtiyas; Adinda Nezma Meidina; Awwa Chaga Qambara Taqwa
SCRIPTA SCORE Scientific Medical Journal Vol. 8 No. 1 (2026): SCRIPTA SCORE Scientific Medical Journal
Publisher : Talenta Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32734/scripta.v8i1.26035

Abstract

Background: Human Immunodeficiency Virus (HIV) remains a major global health challenge with high morbidity and mortality rates. Although antiretroviral therapy (ART) effectively suppresses viral replication, it is unable to eradicate latent HIV reservoirs, preventing complete viral clearance. Advances in genome editing technologies, particularly Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR-Cas9), have created new opportunities for HIV treatment through the targeted elimination of integrated viral genetic material. Objective: This study aimed to review the potential of CRISPR-Cas9 conjugated with extracellular vesicle delivery systems as a therapeutic strategy for HIV based on current scientific evidence. Methods: A literature review was conducted using scientific articles retrieved from PubMed, ScienceDirect, NCBI, and other relevant scientific databases. Relevant studies were critically reviewed and synthesized to evaluate its therapeutic potential for HIV treatment. Discussion: The findings indicate that CRISPR-Cas9 can target multiple stages of the HIV life cycle, including disruption of viral entry coreceptors, inhibition of viral replication, and elimination of latent proviral DNA integrated within host genomes. Furthermore, extracellular vesicles offer several advantages as delivery vehicles, including high biocompatibility, low immunogenicity, and efficient intracellular delivery of CRISPR-Cas9 components. Several studies have demonstrated that the combination of CRISPR-Cas9 and extracellular vesicle-based delivery systems can reduce HIV proviral expression and prevent the reactivation of latent viral reservoirs. Conclusion: CRISPR-Cas9 conjugated with extracellular vesicle delivery systems represents a promising therapeutic approach for HIV treatment. However, further studies are required to evaluate its safety, efficacy, and clinical applicability in humans. Keywords: CRISPR-Cas9, extracellular vesicles, gene therapy, genome editing, HIV.   Latar Belakang: Human Immunodeficiency Virus (HIV) masih menjadi tantangan kesehatan global dengan angka morbiditas dan mortalitas yang tinggi. Meskipun terapi antiretroviral (ART) efektif dalam menekan replikasi virus, terapi ini belum mampu mengeliminasi reservoir laten HIV sehingga belum dapat memberikan kesembuhan secara menyeluruh. Perkembangan teknologi genome editing, khususnya Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR-Cas9), membuka peluang baru dalam terapi HIV melalui eliminasi materi genetik virus yang terintegrasi pada genom inang. Tujuan: Mengkaji potensi CRISPR-Cas9 yang dihantarkan menggunakan vesikel ekstraseluler sebagai strategi terapeutik HIV berdasarkan bukti ilmiah terkini. Metode: Penelitian ini menggunakan metode literature review dengan menelaah berbagai artikel ilmiah yang diperoleh dari PubMed, ScienceDirect, NCBI, dan sumber ilmiah relevan lainnya. Artikel yang relevan ditelaah secara kritis dan disintesis untuk mengevaluasi potensi terapeutik pendekatan tersebut dalam pengobatan HIV. Pembahasan: Kajian menunjukkan bahwa CRISPR-Cas9 mampu menargetkan berbagai tahap siklus hidup HIV, termasuk menghambat koreseptor masuknya virus, mengganggu replikasi virus, serta mengeliminasi provirus laten yang terintegrasi dalam genom sel inang. Selain itu, vesikel ekstraseluler memiliki keunggulan sebagai sistem penghantar karena bersifat biokompatibel, memiliki imunogenisitas rendah, serta mampu meningkatkan efisiensi pengiriman komponen CRISPR-Cas9 ke sel target. Beberapa penelitian menunjukkan bahwa kombinasi CRISPR-Cas9 dan vesikel ekstraseluler mampu menurunkan ekspresi provirus HIV dan menghambat aktivasi ulang reservoir laten. Kesimpulan: CRISPR-Cas9 yang dihantarkan menggunakan vesikel ekstraseluler berpotensi menjadi strategi terapeutik inovatif untuk HIV. Meskipun demikian, penelitian lebih lanjut masih diperlukan untuk mengevaluasi keamanan, efikasi, dan aplikasinya pada manusia. Keyword: CRISPR-Cas9, HIV, penyuntingan genom, terapi gen, vesikel ekstraseluler.
Vaksin Berbasis Messenger Ribonucleic Acid (mRNA) untuk Pencegahan Human Immunodeficiency Virus (HIV): Perkembangan Teknologi dan Bukti Klinis Terkini Muhammad Rizky Hidayatullah; Adinda Nezma Meidina; Salwa Adilah Ningtiyas; Awwa Chaga Qambara Taqwa
SCRIPTA SCORE Scientific Medical Journal Vol. 8 No. 1 (2026): SCRIPTA SCORE Scientific Medical Journal
Publisher : Talenta Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.32734/scripta.v8i1.26037

Abstract

Background: Human Immunodeficiency Virus (HIV) remains a major global public health challenge. According to the World Health Organization (WHO), in 2025, approximately 41 million people were living with HIV, with an estimated 570,000 deaths attributable to HIV-related causes and 1.2 million new HIV infections. These figures underscore the importance of effective HIV prevention strategies. Messenger ribonucleic acid (mRNA)-based vaccines represent a promising platform for HIV prevention because they enable flexible delivery and expression of HIV immunogens. Objective: To evaluate the development and potential of mRNA-based vaccines for HIV prevention. Methods: A narrative literature review was conducted using the Cochrane Library, Europe PMC, PubMed, ScienceDirect, Semantic Scholar, SpringerLink, Wiley Online Library, and Google Scholar for publications from 2021 to 2026. A total of 17 peer-reviewed articles were included and narratively synthesized. Results: Preclinical studies and phase I trials demonstrated that mRNA-LNP vaccines can induce HIV-specific humoral and cellular immune responses. In macaques, one candidate reduced the risk of heterologous SHIV infection by 79% per exposure. In humans, IAVI G002 and G003 demonstrated activation and early maturation of VRC01-class bnAb precursors, while HVTN 302 induced autologous tier 2 neutralizing antibodies in 80% of recipients receiving membrane-anchored Env trimers compared with 4% receiving soluble trimers. However, current evidence has not demonstrated that mRNA vaccines can prevent HIV acquisition in humans, induce broad and durable bnAb responses, or provide protection against viral diversity. Conclusion: mRNA-based HIV vaccines demonstrate biological feasibility and promising early clinical immunogenicity, but their protective efficacy has not yet been established. Further clinical studies are warranted to optimize delivery systems, dosing, durability of immune responses, and long-term safety. Keyword: antibodies; HIV prevention; immunogenicity; mRNA vaccine   Latar Belakang: Human Immunodeficiency Virus (HIV) masih menjadi masalah kesehatan masyarakat global. Menurut World Health Organization (WHO), pada tahun 2025 diperkirakan terdapat 41 juta orang yang hidup dengan HIV, dengan sekitar 570.000 kematian akibat penyebab terkait HIV dan 1,2 juta infeksi baru. Hal ini menunjukkan pentingnya pencegahan HIV. Vaksin berbasis messenger ribonucleic acid (mRNA) merupakan salah satu platform yang berpotensi dikembangkan untuk pencegahan HIV karena memungkinkan penghantaran dan ekspresi imunogen secara fleksibel. Tujuan: Mengevaluasi perkembangan dan potensi vaksin berbasis mRNA untuk pencegahan HIV. Metode: Penelitian ini menggunakan narrative literature review. Pencarian literatur dilakukan melalui Cochrane Library, Europe PMC, PubMed, ScienceDirect, Semantic Scholar, SpringerLink, Wiley Online Library, dan Google Scholar terhadap publikasi tahun 2021–2026. Sebanyak 17 artikel ilmiah peer-reviewed yang memenuhi kriteria inklusi disintesis secara naratif. Hasil: Penelitian praklinis dan uji fase I menunjukkan bahwa mRNA-LNP dapat menginduksi respons imun humoral dan seluler spesifik HIV. Pada kera, salah satu kandidat menurunkan risiko infeksi SHIV heterolog sebesar 79% per pajanan. Pada manusia, IAVI G002 dan G003 menunjukkan aktivasi serta pematangan awal prekursor bnAb kelas VRC01, sedangkan HVTN 302 menghasilkan antibodi penetral tier 2 autolog pada 80% penerima trimer Env membrane-anchored dibandingkan 4% pada trimer terlarut. Namun, bukti yang tersedia belum menunjukkan kemampuan vaksin mRNA dalam mencegah akuisisi HIV pada manusia, menghasilkan respons bnAb yang luas dan persisten, atau memberikan perlindungan terhadap keragaman virus. Kesimpulan: Vaksin HIV berbasis mRNA menunjukkan kelayakan biologis dan imunogenisitas klinis awal, tetapi efikasi protektifnya belum terbukti. Diperlukan uji klinis lebih lanjut untuk mengoptimalkan sistem penghantaran, dosis, durabilitas, dan keamanan jangka panjang. Kata kunci: antibodi; pencegahan HIV; respons imun; vaksin mRNA.
Co-Authors Adinda Nezma Meidina Muhammad Rizky Hidayatullah Salwa Adilah Ningtiyas